Physio Flashcards
What are the three forms of CO2 in the blood?
Dissolved
bicarbonate (HCO3)
Carbamino compounds (CO@ combined with hemoglobin or other blood proteins)
What is the anion gap and how is it calculated?
Difference between all measured cations and anions in plasma. There are more measurable cations than anions.
Cations = NA, K , Mg, CA
Anions - Cl, biocarb, albumin, organic acids, phosphate, sulfate
Simplified equation
(NA+K) - (Cl+bicarb)
Normal in dogs - 12-24 mEq/L
Normal in cats - 13-27 mEq/L
What is the strong ion gap?
Strong ions - ions that fully dissociate at physiologic pH
Strong ion gap - difference between all measured plasma strong cations and anions
It increase with an increase in unmeasured strong anions
It measures increases in strong anions while accounting for concentrations of buffering anions (e.g. plasma proteins and phosphate) IT may be more sensitive for animals with multiple disorders affecting acid base Status
How is the strong ion gap calculated and what is a normal strong ion gap?
Dog SIG = Albumin x 4.9 - calculated anion gap
Cat SIG = albumin x 7.4 - calculated anion gap
Normal values for dogs and cats = -5 to +5 mEq/L
A low PaCO2 would suggest what/ do what to blood pH?
Respiratory alkalosis, hyperventilation
If PaCO2 is >35 mmHg, what does this suggest?
Hypoventilation, respiratory acidosis
A bicarb of 15 suggests what?
Metabolic acidosis
A bicarb of 30 suggests what?
Metabolic alkalosis
Is it possible to overcompensate for a primary problem?
No it is not possible, if it looks like there is overcompensation, then there is likely a mixed acid base disorder
What would you expect to occur during a metabolic acidosis with respiratory compensation?
Decreased pH, decreased CO2 (compensatory respiratory alkalosis), decreased bicarb
What are examples/ causes of a high anion gap metabolic acidosis? What about a normal anion gap acidosis?
High anion gap acidosis — Results from accumulation of excess anions via gain of acid — examples DKA, lactic acidosis, uremic acidosis, intoxication’s (ethylene glycol, metaldehyde, salicylates)
Normal anion gap acidosis — results from loss of bicarb or retention of H with associated hyperchloremia (Addisons, diarrhea, RTA, post hypocapnia, iatrogenic (carbonic anhydride inhibitors, ammonium chloride, protein portion of TPN)
What would you expect to occur during a respiratory acidosis with metabolic compensation?
Increased CO2, decreased pH, compensatory INCREASE in bicarb
What are potential causes of a respiratory acidosis?
Airway obstruction, small airway disease, pulmonary parenchyma disease (pneumonia, heart failure ,etc)
Restrictive pleural space disease (pneumothorax, Pyo, etc)
Neuromuscular disease (hypoventilation)
Increased CO2 production with concurrent heat stroke
Iatrogenic (underventilation under GA)
Marked obesity
What would you expect to occur with metabolic alkalosis with compensation?
Increased pH, increased bicarb, increased CO2 (compensatory respiratory acidosis)
What are differentials for a metabolic alkalosis?
Hypochloremic alkalosis - loop/thiazide diuretics, vomiting, iatrogenic (bicarb therapy)
Concentration alkalosis — pure water loss, hypotonic fluid loss
Chloride resistant alkalosis - hyperadrenocorticism, hyperaldosteronis
Hypoalbuminemic alklaosis - PLE, PLN, synthetic liver failure
What would expect to occur with respiratory alkalosis with metabolic compensation?
Decreased CO2, decreased bicarb (compensatory metabolic acidosis), increased pH
What are Ddx for a respiratory alkalosis?
Hypoxemia - stimulation of peripheral chemoreceptors that increase drive to breathe/ hyperventilation
Nonhypoxemic activation of pulmonary stretch/ novice-tours - PTO, pulmonary fibrosis, pulmonary edema
Activation of central respiratory centers
Iatrogenic - mechanical over ventilation
Sepsis, fever, fear, pain, anxiety
For a metabolic acidosis, for every 1 mEq/L decrease in bicarb, in a dog how much would expect the PCO2 to decrease to compensate?
PCO2 should decreased by 1 mmHg by every 1 mEq/L drop in bicarb
Cats DO NOT compensate
For a respiratory acidosis/ for every 1 mmHg increase in PCO2, how much would expect the bicarb to increase to compensate over time for a dog and cat?
What is the expected respiratory compensation for a metabolic alkalosis?
PCO2 should increase by 0.7 mmHg in the dog and cat
For a respiratory alkalosis for every 1 mmHg drop in PCO2, what is the expected metabolic compensation in the dog and cat?
Acute in dog and cat - HCO3 decreases by 0.25 mEq/L
Chronic in dog and cat - HCO3 decreases by 0.55 mEq/L
When might you suspect a mixed acid base disorder?
Over compensation for a primary problem
OR compensation is of lesser than expected magnitude
What are differentials for a patient that is volume overloaded and is hypernatremic?
(I.e. impermeable solute gain)
Salt poisoning, hyperaldosteronism, hypertonic fluid administration
What are differentials for a patient that is euvolemic with evidence of hypernatremia?
Indicates a pure water deficit
- Primary hypodipsia
- Central DI
- nephrogenic DI (primary or secondary)
- High environmental temperature
- Fever
- Inadequate water access
What are differentials for hypernatremia in a patient that is assessed to be hypovolemic?
Extrarenal — GI: vomiting, diarrhea, small intestinal obstruction, Third space loss: pancreatitis peritonitis, Cutaneous: burns
Renal causes: appropriate: osmotic diuresis (mannitol, hyperglycemia), chemical diuresis (furosemide, ethacrynic acid)
Inappropriate: chronic renal failure,nonoliguric acute renal failure, post obstructive diuresis
How is a pure water deficit treated?
D5W
Formula for correction over 48 hours with goal of not changing serum sodium concentration faster that 0.5 mEq/kg/hr
Current weight x (current Na/ normal Na - 1)
Can also consider treatment with loop diuretic to promote sodium excretion and help normalize ECF volume
What breed may have congenital central DI?
Afghan hounds
What are potential causes of primary nephrogenic DI?
V2 receptor mutations (Huskies)
AQP2 channel mutation
What are potential causes of secondary NDI?
Drugs - steroids, lithium, E. Coli endotoxin, diuretics
Electrolyte disturbances - hypokalemia, hypercalcemia
Altered medullary hypertonicity - hypoadrenocorticism
Multifactorial/ unknown mechanism - hepatic insufficiency, hyperthyroidism, hyperadrenocorticism
Post obstructive diuresis
Acromegaly
Medullary interstitial amyloidosis
Poly cystic kidney disease
Chronic pyelonephritis
Chronic interstitial nephritis
How is nephrogenic DI treated?
Correct underlying cause
If primary: dietary sodium restriction
Thiazide diuretics - used to induce mild dehydration ,enhanced proximal renal tubular resorption of sodium, decreased delivery of tubular fluid to distal nephron and reduced urine output
What are differentials for hyponatremia in a patient with normal plasma osmolality?
Hyperlipidemia, hyperproteinemia (I.e. pseudo hyponatremia)
What are differentials for hyponatremia in a patient with low plasma osmolality?
Hypervolemia: severe liver disease, CHF, nephrotic syndrome advanced renal failure
Normovolemia: psychogenic polydipsia, SIADH, antidiuretic drugs, myxedema coma, hypotonic fluids
Hypovolemia —
nonrenal - GI loss (vomiting, diarrhea), third space loss (pancreatitis, peritonitis, pleural effusion, uroabdomen)
REnal route - hypoadrenocorticism, diuretic administration
What might cause hyponatremia in a patient that has a high plasma osmolality?
Hyperglycemia, mannitol infusion — increased presence of sodium free solute draws fluid into the intramuscular space
Each 100 mg/dL glucose reduces Na by 2.4 mEq/L
Why does hypervolemic hyponatremia occur?
RAAS overactivation due to severe liver disease, CHF, nephrotic syndrome, advanced renal disease, etc
ADH release
Primary intrarenal sodium retention. - found occurring due to nephrotic syndrome only (based on normal renin and aldosterone levels in certain patients with nephrotic syndrome)
What is a potential risk when too quickly correcting severe hyponatremia?
Osmotic demyelination - when hyponatremia is corrected faster than the brain can re-establish idiogenic osmoles
What are diagnostic criteria for SIADH?
Inappropriately high urine osmolality in the presence of plasma hypoosmolality
Normal adrenal, renal ,and thyroid function
Presence of natriuresis despite hyponatremia and plasma hypoosmolality as a result of mild volume expansion
No evidence of hypovolemia
No evidence of ascites or edema
Correction of hyponatremia with fluid restriction
What is cerebral salt wasting syndrome?
Occurs in people with intracranial injury, differentiated from SIADH as water and sodium replacement are needed in cerebral salt wasting syndrome while water restriction is needed for SIADH
Caused by atrial and brain natriuretic factors
Treatment = fluid therapy and fludricortisone (Facilitates sodium retention)
The overall pathophysiology of DIC is characterized by?
- Increased thrombin production
- Suppression of physiologic anticoagulant pathways
- Impaired fibrinolysis
- Activation of inflammatory pathways
What is the main initiator of DIC?
Tissue factor (aka TF, coagulation factor III, tissue thromboplastin
It is expressed on monocytes and endothelial cells within circulation during inflammation and on malignant cells in cancer patients
It is a transmembrane protein that is not typically exposed to general circulation, but increased exposure to circulation leads to DIC
It is released into circulation in response to pro-inflammatory cytokines (they induce monocytes/ macrophages to express tissue factor)
Which pro inflammatory cytokines may induce expression of tissue factor, precipitating DIC?
IL 1 - increases platelet reactivity, increases TF expression in vitro, most procoagulant changes occur before detectable in Vito
Il6 - principle mediator of coagulation activation
TNFa - influences coagulation directly through its effects on IL6. Can also perpetuate inflammation by induction of NFkB —> TNFa
Endotoxin
What else other than inflammatory cytokines can lead to increased tissue factor exposure?
Systemic infection, trauma, burns, heatstroke, cancer
What is the main stimulus for coagulation in Vivo?
Tissue factor: factor VII a complex (in the extrinsic pathway)
What happens following formation of the tissue factor: factor VIIa complex?
This activates factor IX (intrinsic) and factor X (extrinsic)
Activated factor X generates thrombin
Thrombin activates factor XI, VII, and V, thus amplifying its own production
Once thrombin formation occurs, what does it do to fibrinogen?
Converts fibrinogen to fibrin, which forms strands to support clots
How do platelets promote pro coagulation?
They can alter their morphology and express negatively charged substances on their surface, which enhance prothrombinase and tease
They can increase their number of copies of active fibrinogen receptor
Secrete granules with procoagulant elements such as calcium, factor Va, serotonin, fibrinogen, P selection and ADP
What are normal physiologic anticoagulant pathways?
Antithrombin - potent inhibitor of factor IXa, most effective when bound to heparin like GAGs or exogenous heparins (enhances inhibition by 1000 fold), Binds to inhibit thrombin, and factors IXa, Xa, XIa and TF: VIIa
Activated protein C: inhibits factors Va and VIIIa. Effects are enhanced 20 fold when in the presence of protein S. IT prevents thrombin from acting on fibrinogen and platelets. Also produces thrombin activatable fibrinolysis factor (TAFI)
Tissue factor pathway inhibitor - inhibits TF:VIIa complexes and factor Xa - this is a potent inhibitor of thrombin generation
What is the glycocalyx?
It is a network of glycosaminoglycans (GAGs), proteoglycans, and glycoproteins
—proteoglycans are 50-90% heparin sulfate, which facilitates antithrombin binding and enhances inhibition of thrombin
Other procoagulant also bind to the glycocalyx
The glycocalyx also serves as a mechanoreceptor, sensing altered blood flow and releasing nitric oxide during times of increased shear stress to maintain appropriate organ perfusion
Why is fibrinolysis impaired during DIC?
Activation of fibrinolysis occurs concurrently with thrombin generation - there is an initial rapid increased in fibrinolytic activity during sepsis/SIRS secondary to release of tissue plasminogen activators from endothelial cells. TPA —> plasminogen —> plasmin —> cleavage of fibrin clot. Increase in plasmin activated complement and kin in systemic which can lead to shock, hypotension, and increased vascular permeability. This results in increased fibrin degradation products (FDPs) from fibrinogen or cross linked fibrin strands).
D diners come from cross linked fibrin, FDPs coat platelets to prevent hemostasis and interfere with fibrin polymerization.
During DIC, fibrin deposition surpasses fibrinolysis
How does activation of inflammatory pathways contribute to the pathogenesis of DIC?
Inflammatory pathways upregulate TF expression and downregulate inhibitors
Activated coagulation proteins stimulate release of inflammatory cytokines
Endothelial cells can be activated by inflammatory cytokines (TNFa, bradykinin, thrombin, histamine, and VEGF) —> activated endothelial cells release ultralarge VWF, which increases platelet tethering and activation at site of activated endothelial cells. There is also a decrease in ADAMTS13 (which usually cleaves ULVWF into smaller particles and makes it less potent)
Platelet activating factor is also released from inflammatory cells
Protein C system is depressed during DIC, so anti inflammatory effects of protein C system are lost
What are tests to diagnose DIC of increase clinical index of suspicion for DIC?
PT/PTT prolongation (PTT is more sensitive indicator due to greater consumption of these factors in DIC)
Fibrinogen can be increased or decreased in DIC
Degree of thrombocytopenia - continued platelet decrease even within RI is suggestive of thrombin generation
D dimer elevation - (this results from plasmin degradation of cross linked fibrin and is specific for fibrinolysis not DIC (can also see increased D diners in thromboembolic disease, trauma, surgery, hemorrhage and neoplasia)
The Best combination of tests to obtain the most accurate diagnosis of DIC=. Platelets, aPTT, FDP, D dimer — sensitivity of 73%, specificity of 97%
What can result in elevated fibrin degradation products?
Elevated FDPs do not distinguish between degradation product of fibrinogen or cross linked fibrin
Elevation shows active fibrinolysis, which can occur in trauma, recent surgery, or venous thromboembolism
FDPs are metabolized in the liver and excreted in kidneys - dysfunction in either organ can increased FDP
Is measurement of fibrinogen helpful in confirming DIC?
Not generally, it can remain normal even with high consumption
Sensitivity of fibrinogen for confirming DIC in people is 28-43%
Would you expect antithrombin levels to increase or decrease in DIC?
Decrease - it becomes consumed due to factor activation
Based on a 2018 study measuring thrombin antithrombin complex with a point of care testing device for the diagnosis of DIC, was this test associated with DIC?
Yes, it was positively associated with the severity of DIC
Name the laboratory values that may support a diagnosis of DIC and what changes you would expect to occur
What are the three traditional types of shock?
Hypovolemic
Cardiogenic
Distributive
What are the different forms of shock?
Hypovolemic - decreased effective circulating volume
Distributive - inappropriate vasomotor tone aka vasodilatory shock/ decreased blood flow to vital organs
Cardiogenic shock - decreased forward flow, heart can’t pump enough to periphery
Obstructive shock - decreased forward flow or decreased venous return
Metabolic - abnormal cellular respiration - e,g. Severe metabolic acidosis
Hypoxemic shock - decreased arterial oxygen content
What are compensatory mechanisms for shock?
Peripheral vasoconstriction Increased HR Increased RR RAAS activation ADH release
What are the stages of shock?
Compensatory - cardiac output is increased due to catecholamine release. This is characterized by a normal BP and mild clinical signs (mild tachycardia, injected mm, rapid CRT)
Early decompensatory - blood is preserved for heart and brain perfusion and lactic acidosis and tissue hypoxia occur. This is characterized by hypotension and moderate severe clinical signs (tachycardia, pale mucous membranes, prolonged CRT, depressed mentation and hypothermia)
Late decompensatory shock - auto regulatory escape occurs and the Braine and heart can no longer maintain sympathetic mediated vasoconstriction resulting in global vasodilation and circulatory collapse. This is characterized by severe hypotension and severe life threatening clinical signs (bradycardia, absent CRT, weak or absent pulses, hypothermia, obtundation and oliguria)
What is the Henderson hasselbach equation?
PH can be characterized by changes in bicarbonate and PCO2 (predictable changes in HCO3 occur with loss or gain of H+)
PH = 6.1 +log (HCO3/(0.03 x PCO2))
What is base excess? How is it calculated?
Amount of base above or below the normal buffer base
This is calculated by taking into account the expected change in HCO3 secondary to acute changes in PCO2
Interpretation: HCO3 should rise 1-2 mEq for every acute 10 mmHg increased in pCO2
HCO3 should decrease 1-2 mEq/L for every acute 10 mmHg decrease in PCO2
Why should sodium bicarbonate NOT be used in a patient with respiratory acidosis:?
It exacerbates hypercapnea by donating substrate for carbonic acid equation
How is bicarb dose calculated? When should bicarb be administered?
Administered in severe academia cases - pH <7.15, bicarb < 12
Dose - 0.3 x body weight x base deficit — half of the dose should be given over 6 hours with reevaluation
What are side effects of rapid correction of acidemia with bicarb?
Hyperosmolarity
Hypernatremia
Hypokalemia (alkalosis encourages intracellular shift of potassium)
Ionized hypocalcemia (calcium complexes with bicarb)
Paradoxical CNS acidosis - due to diffusion of CO2 from bicarb administration across the BBB
Name the 5 causes of hypoxemia
Low FiO2 Hypoventilation Diffusion impairment VQ mismatch Pulmonary shunting
What is the difference in arterial PaO2 and SpO2?
PaO2 - measurement of partial pressure of oxygen - provides an estimation of dissolved O2 in the blood
SPO2 - measurement of differences in absorption of two wavelengths of light (red and infrared) by oxygenated and deoxygenated hemoglobin - provides an estimation of hemoglobin saturation.
Which pathological conditions might result in a normal SPO2 reading despite severe hypoxemia?
Carboxyhemoglobinemia and methemoglobinemia
Total body water is what percentage of body weight?
60%
Intracellular fluid is water percentage of total body water?
60%
Extracellular fluid is what percentage of total body water?
40%
What percentage of extracellular fluid volume is interstitial?
75%
What percentage of extracellular fluid volume is intravascular?
25%
How does the endothelial glycocalyx modulate the fluid dynamics of starlings forces (hydrostatic and on optic pressure)?
It maintains vascular permeability
Shield the walls of the blood vessel from direct blood flow exposure
Mediates shear stress dependent nitric oxide production
Promotes retention of vascular protection enzymes (superoxide dismutase)
Perseveres intravascular coagulation inhibition factors (antithrombin, protein C and tissue factor inhibitor)
Modulate the inflammatory response (by preventing leukocyte adhesion and binding of chemo lines, cytokines, and growth factors)
What are mechanisms that prevent extracellular edema?
Finite interstitial volume
Albumin washout
Augmented lymphatic flow
What are the components of FFP? How long is FFP stable for when frozen at -70 C
Stable clotting factors: II, VI, IX, X Labile clotting factors: V and VIII VWF Fibrinogen Albumin - not useful in treating hypoalbuminemia except in small patients due to potential for hypervolemia.
It is stable for 1 year
It is indicated in patients with poor oncotic pressure or patients with coagulopathy
What are the components of fresh plasma?
Stable clotting factors II, VII, IX, X
Fibrinogen
Albumin
