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196 Cards in this Set
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A 17 year old NZ European man presents to the Emergency department complaining of abdominal pain and passing lots of urine. He has vomited twice and is breathing rapidly with deep sighing breaths. The blood glucose is 27 mmol/L and serum ketones are strongly positive.
What is insulin and wheres it made |
peptide hormone produced by beta cells in the pancreas. |
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islets of langerhan cells and hormones produced |
we've learned 3
alpha = makes glucagon (15-20% cell mass) beta cells = makes insulin (65-80%) delta cells = makes somatostatin (3-10%)
glucose or insulin activates B cells and inhibits a cells (paracrine f/b)
glycogen or glucagon activates a cells which activates b and d cells
somatostatin inhibits a cells and b cells
nb theres 2 other types of cells and b cell also makes amylin but dont need to know
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DM px |
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Role of insulin |
Promote uptake of glucose into skeletal muscle and fat and
Inhibit glucose prodxn in the liver
inhibit lipolysis from fat cells
And anabolic ie promote aa uptake into tussues |
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Glycogen stores from where are broken down during periods of low blood glucose |
glycogen stored in the liver and muscles into glucose, which can then be utilized as an energy source |
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Insulin is released when any of several stimuli are detected. These stimuli include |
ingested protein and glucose in the blood produced from digested food. |
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In target cells, insulin initiates a signal transduction, which has the effect of increasing |
glucose uptake and storage |
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Insulin background |
insulin is synthesized in the pancreas within the β-cells of the islets of Langerhans.
1-3 million islets of Langerhans (pancreatic islets) form the endocrine part of the pancreas, which is primarily an exocrine gland.
The endocrine portion accounts for only 2% of the total mass of the pancreas.
Within the islets of Langerhans, beta cells constitute 65–80% of all the cells. |
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Is the pancreas mainly an endocrine organ |
No, 2% is endocrine, the rest is exocrine |
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Does the brain require insulin to uptake glucose |
No, it can do it independently |
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Does the brain require insulin to uptake glucose |
No, it can do it independently |
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Can muscle glycogen be released into the blood in hypoglycemia |
No, only liver glycogen stores are broken down to produce glucose
and the glycerol backbone in triglycerides can also be used to produce blood glucose
Neurones only have a small glycogen store |
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Insulin t=1/2 and breakdown |
1hr breakdown
t=1/2 = 4-6mins
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Effect of insulin on glucose uptake and metabolism. |
Insulin binds to its receptor, which starts many protein activation cascades.
These include translocation of Glut-4 transporter to the plasma membrane and influx of glucose, glycogen synthesis, glycolysis and triglyceride prodxn. |
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The actions of insulin on the global human metabolism level include:
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Control of cellular intake of certain substances, most prominently glucose in muscle and adipose tissue (about two-thirds of body cells)
Increase of DNA replication and protein synthesis via control of amino acid uptake
Modification of the activity of numerous enzymes.
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The actions of insulin (indirect and direct) on cells include: |
Increased glycogen synthesis – insulin forces storage of glucose in liver (and muscle) cells in the form of glycogen;
lowered levels of insulin cause liver cells to convert glycogen to glucose and excrete it into the blood.
This is the clinical action of insulin, which is directly useful in reducing high blood glucose levels as in diabetes.
Increased lipid synthesis – insulin forces fat cells to take in blood lipids, which are converted to triglycerides; lack of insulin causes the reverse.
Increased esterification of fatty acids – forces adipose tissue to make fats (i.e., triglycerides) from fatty acid esters; lack of insulin causes the reverse.
Decreased proteolysis – decreasing the breakdown of protein
Decreased lipolysis – forces reduction in conversion of fat cell lipid stores into blood fatty acids; lack of insulin causes the reverse.
Decreased gluconeogenesis – decreases production of glucose from nonsugar substrates, primarily in the liver (the vast majority of endogenous insulin arriving at the liver never leaves the liver); lack of insulin causes glucose production from assorted substrates in the liver and elsewhere.
Decreased autophagy - decreased level of degradation of damaged organelles. Postprandial levels inhibit autophagy completely.
Increased amino acid uptake – forces cells to absorb circulating amino acids; lack of insulin inhibits absorption.
Increased potassium uptake – forces cells to absorb serum potassium; lack of insulin inhibits absorption.
Insulin's increase in cellular potassium uptake lowers potassium levels in blood. This possibly occurs via insulin-induced translocation of the Na+/K+-ATPase to the surface of skeletal muscle cells.
Arterial muscle tone – insulin forces arterial wall muscle to relax, increasing blood flow, especially in microarteries; lack of insulin reduces flow by allowing these arterial muscles to vasoconstrict.
Increase in the secretion of hydrochloric acid by parietal cells in the stomach
Decreased renal sodium excretion.
Insulin also influences other body functions, such as vascular compliance and cognition.
Once insulin enters the human brain, it enhances learning and memory and benefits verbal memory in particular. Enhancing brain insulin signaling by means of intranasal insulin administration also enhances the acute thermoregulatory and glucoregulatory response to food intake, suggesting that central nervous insulin contributes to the control of whole-body energy homeostasis in humans.
Insulin also has stimulatory effects on gonadotropin-releasing hormone from the hypothalamus, thus favoring fertility. |
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Other substances known to stimulate insulin release include |
the amino acids arginine and leucine, parasympathetic release of acetylcholine (via phospholipase C), sulfonylurea, cholecystokinin (CCK, via phospholipase C), and the gastrointestinally derived incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). |
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role of insulin |
Inhibit glucose prodxn in the liver
And anabolic ie promote aa uptake into tussue |
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insulin synthesis |
first synthesized as preproinsulin in pancreatic B cells, changed in the rER to proinsulin.
Enz's (endopeptidases) cleave proinsulin to insulin releasing a fragment, C-peptide.
insulin is packed in a granule waiting for metabolic signal ie leucine, arginine, glucose and mannose) and vagal nerve stimulation to be exocytosed from the cell into the circulation |
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what metabolic signals or stimulants triggers insulin release |
leucine, arginine, glucose and mannose and vagal nerve stimulation to be exocytosed from the cell into the circulation |
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B cells release insulin in how many phases |
2 phases |
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explain the 1st phase insulin release |
rapidly triggered in response to increased blood glucose levels |
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explain the 2nd phase insulin release |
sustained, slow release of newly formed vesicles triggered independently of sugar |
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insulin release primary mechanism |
glucose enters the B cell through the GLUT2
glucose enters glycolysis and the Kreb cycle = increased ATP
this closes the ATP-sensitive sulfonylurea receptor on B cells, preventing K leave cell = increased K in cell = depol.
this stimulates voltage gated Ca channels to open = raised Ca in cell, stimulates other enzs to ultimately release more Ca from ER = more increase in Ca in cell
this stimulates insulin exocytosis |
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Other substances known to stimulate insulin release include |
amino acids arginine and leucine, PNS release of ACh (via phospholipase C),sulfonylurea, cholecystokinin (CCK, via phospholipase C),
and the gastrointestinally derived incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) |
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Release of insulin is strongly inhibited by the |
stress hormone norepinephrine (noradrenaline) |
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Release of insulin is strongly inhibited by the stress hormone norepinephrine (noradrenaline), which leads to |
increased blood glucose levels during stress |
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It appears that release of catecholamines by the sympathetic nervous system has conflicting influences on insulin release by beta cells - why |
because insulin release is inhibited by α2-adrenergic receptors and stimulated by β2-adrenergic receptors
but the effect of a-adrenergic receptors is greater than B adrenergic receptors resulting in overall inhibition of insulin release |
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Evidence of impaired first-phase insulin release can be seen in |
OGTT |
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A cell starved of insulin in type 1 and 2 DM, what should you expect to see in the px |
weight loss |
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details on post receptor changes on binding of insulin to its receptor |
insulin binds to its receptor (a subunit) = conformational change = activates kinases, phosphorylation cascade results in increased GLUT4 transporters in the plasma membrane.
degradation, endocytosis and degradation of the receptor bound to insulin is a main mechanism to end signaling |
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what are the 3 base types of molecules in metabolism |
aa, carbs and nucleic acids |
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what are the monomer forms of aa, carbs and nucleic acids |
aa, monosac, nucleotides |
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whats the polymer form of aa, carbs and nucleic acids |
proteins (aka polypep), polysac, polynucleotides
eg fibrous protein, starch, DNA respectively |
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compounds that have no metablic use and would be harmful if it got into cells is called what |
xenobiotics eg drugs, natural poisons and antibiotics |
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xenobiotics are detoxified by what |
xenobiotic-metabolizing enzymes eg CYP450 |
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features of glucagon |
made by a cells in |
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glucagon function |
generally increase b/g via gluconeogen/glycogenolysis |
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the liver has glucagon receptors, which when activated by glucagon causes glycogenolysis but what happens when glucagon stores become deplete |
glycogenolysis
as glycogen stores become depleted, glucagon then encourages the liver and kidney to make additional glucose (gluconeogenesis)
glucagon also turns off glycolysis in the liver, encouraging gluconeogen. |
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glucagon also effects lipolysis how |
in induces lipolysis in conditions of insulin suppression ie T1DM
hence regulating the rate of glucose prod. through lipolysis |
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Glucagon production appears to be dependent on the central nervous system through pathways |
yet to be defined |
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an injectable form of glucagon is vital for |
cases of severe hypoglycemia when the victim is unconscious or for other reasons cannot take glucose orally
but it must be reconstituted before use otherwise won't work
dose 1mg |
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anecdotal evidence for BB overdose tx |
glucagon |
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glucagon AE |
common = headache and nausea
interacts with anticoags = increased bleeding |
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adrenaline can also cause increase in b/g true/false |
true?
Contraindicxn for glucagon use with px with PHEO |
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Secretion of glucagon is stimulated by |
* Hypoglycemia * Epinephrine (via β2, α2, and α1 adrenergic receptors) * Arginine * Alanine (often from muscle-derived pyruvate/glutamate transamination (see alanine transaminase reaction). * Acetylcholine[19] * Cholecystokinin |
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Secretion of glucagon is inhibited by |
* Somatostatin * Insulin (via GABA)[20] * PPARγ/retinoid X receptor heterodimer.[21] * Increased free fatty acids and keto acids into the blood * Increased urea prodn |
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autoimmune pathophys
http://www.st-andrews.ac.uk/~gdk/bl4217web/Gp2RefList/autoimmune_path.pdf |
poorly understood as well as the mech. that maintains it
possibly related to immunological tolerance, molecular mimicry/cross reactivity, antibody mediated mechs, cell mediated mechs. |
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Natural self-reactive antibodies are found at low concentration in the serum of |
normal individuals
They usually are of IgM isotype, with low avidity for the antigen |
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ketones are made from what |
FA b/d
made in the liver from FA during low b/g |
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name the 3 ketone bodies |
acetone, acetoacetic acid, and beta-hydroxybutyric acid
nb Other ketone bodies such as beta-ketopentanoate and beta-hydroxypentanoate may be created as a result of the metabolism of synthetic triglycerides such as triheptanoin |
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ketosis vs ketogenesis |
ketosis = metabolic state where body's energy mainly from ketones in blood
ketogenesis = prod. of ketone bodies |
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there are 2 main causes of ketoacidosis |
DKA alcoholic ketoacidosis
less common fasting ketogenic diet (low carb) |
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can ketones be used as an energy source in the heart and brain |
yes, but only acetoacetic acid, and beta-hydroxybutyric acid |
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Ketone bodies are picked up by cells and converted back into |
ACoA goes to citric acid cycle to make energy |
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The heart preferentially utilizes fatty acids for energy under normal physiologic conditions
true/false |
true
even under ketosis, the heart can utilise ketones for energy |
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The brain gets a portion of its energy from ketone bodies when glucose is less available e.g. |
during fasting, strenuous exercise, low carbohydrate, ketogenic diet and in neonates
but the brain has an obligatory r/t for some glucose |
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Acetone is a b/d product of acetoacetate, whats unique about it |
it will b/d if not used and removed as waste or converted to pyruvate
may contribute to weight loss found in ketogenic diets
cannot be converted back to ACoA, so is excreted in urine or exhaled (as a conseq. of high vapor press.) which is responsible for the characteristic sweet and fruity breath in pxs with ketoacidosis |
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what gives pxs with ketoacidosis the sweet and fruity breath |
acetone (which is a ketone) |
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In normal individuals, there is a constant production of ketone bodies by the liver and their utilization by extrahepatic tissue
true/false |
true |
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usu. conc. of ketones in the blood |
1mg/dl |
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normally ketones in the urine are highly detectable |
very low and undetectable |
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ketonemia define |
ketone conc. increases in the blood |
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increased ketones in blood eventually cause |
acidosis
this triggers the kidneys to try excrete the excess glucose and ketones |
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high blood glucose excreted in urine takes what with it |
water and solutes ie Na and K
via osmotic diuresis |
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explain the mech. for polyuria, dehydration and thirst and polydipsia |
hyperglycemia leads to the kidneys trying to excrete excess glucose, which drives osmotic diuresis of water and solutes (ie Na and K)
this leads to polyuria, dehydration, and compensatory thirst and polydipsia |
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ketoacidosis forms what kind of acidosis |
metabolic acidosis |
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in dka what other solutes may be low other than K and Na |
Cl, P, Mg and Ca |
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dka can occur in some t2dm, whats that called and whats the mech. |
ketosis prone type 2 diabetes
exact mech. unclear (?? impaired insulin secrxn/axn) |
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clinically dka is assoc. with release of |
glucagon, adrenaline and cytokines
cytokines leads to increased markers of inflamm. despite no infxn |
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most dangerous complication of DKA |
cerebral edema which can lead to death |
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how does dka lead to dehydration and potassium loss |
usu. lack of insulin and raised glucagon = gluconeogen. in the liver this increased b/g spills over into urine, taking water and solutes with it incl K (osmotic diuresis)
this leads to polyuria, DEHYDRATION, and compensatory polydipsia and thirst. |
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how does dka lead to ketone prodxn |
lack of insulin also leads to the release of FFA from adipose tissue (LIPOLYSIS)
which is converted in the liver to ketones |
http://en.wikipedia.org/wiki/Diabetic_ketoacidosis |
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hyperosmolar non-ketotic syndrome aka |
hyperosmolar non-ketotic coma (HONK),
nonketotic hyperosmolar coma,
Hyperosmolar hyperglycemic state |
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HNKS - Hyperosmolar hyperglycemic state is mainly experienced in what type of diabetes |
mainly t2 |
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hyperosmolar non ketotic syndrome is a complication of mainly t2dm related to what |
high blood sugars cause SEVERE DEHYDRATION, increases in osmolarity and high risk of coma and death |
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how is HNKS different from dka |
no ketones |
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how is HNKS dx |
* Plasma glucose level GT 600 mg/dL (GT 30 mmol/L) * Serum osmolality GT 320 mOsm/kg * Profound dehydration, up to an average of 9L (and therefore substantial thirst (polydipsia)) * Serum pH >7.30 * Bicarbonate >15 mEq/L * Small ketonuria (~+ on dipstick) and absent-to-low ketonemia (<3 mmol/L) * Some alteration in consciousness |
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tx for HNKS |
correct dehydrxn with IV fluids
reduce b/g with insulin
and mgmt of any precipitating illness eg antibiotics for infxn |
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generally what to look at to dx HNKS |
plasma glucose serum osmolality volume status serum pH bicarb ketonuria altered LOC |
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additional sx/signs of HNKS |
focal neuro. signs ie sensory/motor deficits; focal seizures/motor abn.
hyperviscosity and increased risk of blood clot formxn |
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hyperviscosity of blood can be seen in what condxns |
generally those with increased cell numbers eg polycythemia (tx=phlebotomy), leukemia (same tx above), multiple myeloma (tx = plasmapheresis) |
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pathophys of HNKS |
usu. precipitated by infxn, MI, stroke or another acute illness
relative insulin def. or resistance = high b/g and serum osmolarity = osmotic diuresis resulting in excess urination (polyuria) = dehydration and subseq. increase b/g conc. (cause of dehyd)
remember no ketosis bcuz theres still some insulin which inhibits lipolysis |
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CO2 + H2O = H2CO3 = HCO3- + H+
what does this represent |
bicarb. buffering sys
nb carbonic anhydrase catalyses the rxn of CO2 + H2O to carbonic acid |
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the bicarbonate buffering system in rbcs is a fast way to regulate pH in the body
yes/no |
yes
slower mech. = renal compensation |
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hypervent. causes what |
loss of CO2 and thus a reduxn in acidosis (ie try to normalise pH) |
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Henderson–Hasselbalch equation can be used to relate the pH of blood to constituents of the |
bicarbonate buffering system |
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hypoventilation will affect CO2 how |
increase it |
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hypoventilation will raise CO2, how will that affect pH |
decrease it ie acidosis |
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acute respiratory acidosis vs chronic resp. acidosis |
both have raised PaCO2
but acute pH = acidosis
chronic pH = normal/near-normal due to 2o renal compensation + raised bicarb. |
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acute resp. acidosis causes |
failure of vent. or can't vent. adeq. or a/w obstrxn |
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acute resp. acidosis causes
failure of vent. |
depression of the central respiratory center by cerebral disease or drugs |
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acute resp. acidosis causes
inability to ventilate adequately
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due to neuromuscular disease
eg myas. gravis, ALS, GBS, muscular dystrophy |
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acute resp. acidosis causes
airway obstruction |
related to asthma or COPD exacerbation |
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chronic resp. acidosis causes |
maybe secondary to * COPD,* obesity hypovent. synd, * neuromascular disorders (check acute list), * ILD and * thoracic deformities |
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central respiratory centers, which are located in the |
pons and medulla |
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Ventilation is influenced and regulated by chemoreceptors for PaCO2, PaO2, and pH located in the |
brainstem,and in the aortic and carotid bodies as well as by neural impulses from lung stretch receptors and impulses from the cerebral cortex. |
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failure of ventilation quickly increases |
PaCO2 |
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In acute respiratory acidosis, compensation occurs in 2 steps |
1) cellular buffering over mins-hrs =slight increase in plasma bicarb
2) renal compensation occurs over 3-5 days = increase carbonic acid excretion and bicarb resorp increased |
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give an example of how renal compensation increases bicarb |
PEPCK is upregulated in renal proximal tubule brush border cells, in order to secrete more NH3 and thus to produce more HCO3− which gets resorbed |
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in renal compensation, plasma bicarb increases are proportional to what increases in PaCO2 |
3.5mEq/L bicarb rise for every 10mmhg PaCO2 rise
estimate |
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does resp acidosis have a great effect on electrolyte levels e.g K+, Ca |
No, some small effects incl:
acidosis decreases binding of Ca to Albumin and tends to increase serum ionized Ca
also, it causes an K+ to move out of cells (but rarely causes hyperK) |
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define metabolic acidosis |
occurs when the body produces excess acid or when the kidneys are not removing enough acid from the body |
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main causes of met. acid. are best grouped by their influence on the anion gap |
increased or normal AG |
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anion gap notes |
it might be normal due sampling error eg excess triglycerides
might be increased due to low levels of cations other than Na/K eg Ca/Mg |
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metabolic acidosis causes based on
increased anion gap |
lactic acidosis
ketoacidosis
chronic renal failure (accumulation of sulfates, phosphates, urea)
intoxication: -organic acids (salicylates, ethanol, methanol, formaldehyde, ethylene glycol, paraldehyde, INH) - sulfates, metformin (Glucophage)
massive rhabdomyolysis |
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metabolic acidosis causes based on
increased anion gap |
lactic acidosis
ketoacidosis
CKF
Intoxication
Massive rhabdomyolysis |
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metabolic acidosis causes based on
increased anion gap
MUDPILES |
* M-Methanol * U-Uremia (chronic kidney failure) * D-Diabetic ketoacidosis * P-Propylene glycol ("P" used to stand for Paraldehyde but this substance is not commonly used today) * I-Infection, Iron, Isoniazid, Inborn errors of metabolism * L-Lactic acidosis * E-Ethylene glycol (Note: Ethanol is sometimes included in this mnemonic as well, although the acidosis caused by ethanol is actually primarily due to the increased production of lactic acid found in such intoxication.) * S-Salicylates |
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metabolic acidosis causes based on
increased anion gap
CKF (chronic kidney faillure) |
accumulation of: sulfates, phosphates, urea |
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metabolic acidosis causes based on
increased anion gap
intoxication |
organic acids (salicylates, ethanol, methanol, formaldehude, ethylene glycol, paraldehyde, INH)
sulfates, metformin |
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metabolic acidosis causes based on
normal anion gap causes |
longstanding diarrhea (bicarbonate loss)
bicarbonate loss due to taking topiramate
pancreatic fistula
uretero-sigmoidostomy
Renal tubular acidosis (RTA)
intoxication: * ammonium chloride* acetazolamide (Diamox) * bile acid sequestrants * isopropyl alcohol
renal failure (occasionally)
inhalant abuse
toluene |
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metabolic acidosis causes based on
normal anion gap common causes? |
longstanding diarrhoea
renal failure
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The body regulates the acidity of the blood by four buffering mechanisms |
* bicarbonate buffering system * Intracellular buffering by absorption of hydrogen atoms by various molecules, including proteins, phosphates and carbonate in bone. * Respiratory compensation * Renal compensation |
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what can cause K to move our of cells
review in U2D - potassium balance in acid-base disorders |
acidosis ie excess H+ low insulin BB digoxin |
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hx for acute t1dm px |
polyuria polydipsia xerostomia (dry mouth) polyphagia (increased hunger) lethary smell of acetone weight loss nausea and vommiting abdo. pain kussmaul breathing (hypervent.) |
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signs and symptoms of diabetic ketoacidosis |
xeroderma (dry skin), rapid deep breathing, drowsiness, abdominal pain, vomiting, weight loss |
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with this 17 yo px presenting for the first time with abdo. pain, polyuria, vommiting with deep sighing breathing (kasmaul breathin) and b/g of 27mmol/L and sKetones +ve
is this a medical emergency |
yes, px likely to be in diabetic ketoacidosis
likely due to T1DM, |
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with this 17 yo px presenting for the first time with abdo. pain, polyuria, vommiting with deep sighing breathing (kasmaul breathin) and b/g of 27mmol/L and sKetones +ve
common ddx |
dka t1dm acute kidney injury HNKS (more common in t2dm)
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with this 17 yo px presenting for the first time with abdo. pain, polyuria, vommiting with deep sighing breathing (kasmaul breathin) and b/g of 27mmol/L and sKetones +ve
less common ddx but important not to miss |
lactic acidosis, severe sepsis, aspirin overdose, massive rhabomyolysis, ethylene glycol poisoning, paraldehyde, methanol or formaldehyde poisoning
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with this 17 yo px presenting for the first time with abdo. pain, polyuria, vommiting with deep sighing breathing (kasmaul breathin) and b/g of 27mmol/L and sKetones +ve
uncommon ddx |
renal tubular acidosis types 1 and 2, glue sniffing |
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most common sxs for T1DM |
polyuria, polydipsia, and polyphagia, along with lassitude, nausea, and blurred vision, all of which result from the hyperglycemia itself. |
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signs for this px presenting for first time with what sounds like a dka |
for new presentations theres usu. no abn. signs but with they have dka, they might have
Kussmaul respiration, signs of dehydration, hypotension, and, in some cases, altered mental status |
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how to distinguish b/w HNKS and dka
remember than dka can occur in both but is more common in t1dm and hnks can occur in both but is more common in t2dm |
HNKS b/g levels are usu. much higher than in dka ie GT 40-50mmol/L metabolic acidosis is absent or mild altered mental state more common here tends to affect elderly
dka lower spike in b/g dka is a metabolic acidosis |
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distribution of total body water based on 70 kg body weight
how much would be total body water |
weight x 60% = 42 litres |
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total body water is made up of two fluid compartments - what |
ECF and ICF |
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how much fluid in ICF |
weight x 40% = 28L (remember 70kg person) |
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how much fluid in ECF |
weight x 20% = 14L |
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ICF comprises what compartments |
nothing, buck stops here |
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ECF comprises what compartments |
ISF and IVF (intravascular fluid) |
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how much water in ISF |
weight x 15% of ECF (14L) = 11L |
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how much water in IVF |
weight x 5% of ECF (14L) = 3L |
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in all of the different fluid compartments of the body - are all the membranes (ie cell membranes, bv endothelium) permeable to WATER AND SOLUTES |
ONLY WATER EVERYTHING ELSE IS REGULATED |
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Distribution of electrolytes and protein in
ICF |
Na = 12 K = 150
PO4 = 116 Protein = 40 Cl = 3 |
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Distribution of electrolytes and protein in
ISF |
Na = 140 K = 4
PO4 = 2 Protein = 5 Cl = 103 |
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Distribution of electrolytes and protein in
IVF (intravascular fluid) aka plasma distribution of electrolytes and proteins |
Na = 140 K = 4
PO4 = 2 Protein = 16 Cl = 103 |
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in general what is the distribution of electrolytes and protein in ICF AND ECF - ISF and IVF/PLASMA |
Na mostly in the ECF K mostly in ICF PO4 mostly in ICF Protein mostly in ICF Cl is mostly in the ECF |
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whats the relevance of the different water compartments, electrolyte and protein distribution |
clinically it can help you determine the distribution of IV fluid |
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How much Na and Cl in .9% NaCL |
0.9% NaCl has Na 154mmol and Cl 154mmol |
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what happens if you infuse 1000ml of .9% NaCL IV
how much of it will expand the plasma volume |
1. it distributes evenly throughout the ECF ie equal amount in plasma/IVF and ISF
2. All the Na remains in the ECF
3. since Na and Cl are not allowed to enter the cell, there is no water movement into the cell |
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if you infuse 1000ml of .9% NaCL IV
how much of it will expand the plasma volume |
plasma/IVF = 3L
ECF total water = 14L
IV infusion = 1000ml
(3/14) x 1000ml = 214ml |
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what happens to the bodies water compartments when you give 1000ml 5% dextrose |
1. it distributes evenly through ECF ie IVF/plasma and ISF
2. dextrose take up into cells and metabolised thus losing its osmotic potential
3. leaves 1000ml free water in the ECF and osmotic imbalance b/w ICF and ECF, so water enters cells (not all) |
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when you give 1000ml 5% dextrose how much of it will expand the plasma volume |
plasma/IVF = 3L
total body water = 42L
fluid infusion = 1000ml
Plasma (3/42) x 1000 ml = 71 ml |
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fluid and electrolyte reqts
daily water balance (for 70kg person) |
you consume or produce (via metabolism) water which is roughly 2.3L
you lose water via skin, lungs, sweat, urine, faeces or roughly 2.3L
so you need to drink about 2-2.3L/day |
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fluid and electrolyte reqts
daily water balance (for 70kg person) - explain the distribution through the body of ingested/metabolic water |
it goes into ECF and get even distribution into ICF or try and reach an equilibrium
what water is lost is done through the ECF |
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fluid and electrolyte reqts
daily water balance (for 70kg person) - waters the breakdown of water into the ECF |
Ingested fluid 2100ml Metabolic water 200ml |
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fluid and electrolyte reqts
daily water balance (for 70kg person) - waters the breakdown of water out of the the ECF |
Skin 350ml Lungs 350ml Sweat 100ml Urine 1400ml Faeces 100ml |
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fluid and electrolyte reqts
daily water balance (for 70kg person) - where is most of the gained and where is it mostly lost |
ingested fluid = 2100ml
urine = 1400ml |
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how much fluid do we need to drink roughly per day to help replete our total water stores |
2-2.5L/day |
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how to Estimate usual daily fluid requirement |
1.5ml / kg /hr = 1.5 x 70 x 24 = 2520
about 2.5L/day |
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daily electrolyte req/ts for Na and K |
Na+ 0.5 - 1.0 mmol/kg/day
K+ 0.5 mmol/kg/day |
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high serum osmolality is most commonly due to |
most common are alcohols (ethanol, methanol, isopropanol, ethylene glycol), mannitol and glycine |
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Vasopressin release is stimulated by any of the following: |
*
Increased plasma osmolality * Decreased blood volume * Decreased BP * Stress |
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drinking water does what to plasma osmolality |
decreases it
Low plasma osmolality inhibits vasopressin secretion, allowing the kidneys to produce dilute urine |
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are most fluid infusions designed to be iso-osmolar |
yes |
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define colloid |
fluid with protein like mass |
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define crystalloid |
ionic solution |
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.9% NaCL is aka |
normal saline |
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features of .9% NaCl aka normal saline |
Crystalloid Isotonic First line resuscitation fluid Used for expanding ECF and plasma • Ratio ~4:1 for plasma expansion Used for replacing high sodium losses • Esp proximal GIT (eg NG drainage, vomiting) |
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is normal saline crystalloid or colloid |
crystalloid |
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is normal saline intended to make cells swell/shrink |
no, cuz isotonic |
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clinically normal saline is used as a |
1st line resus fluid
used to expand ECF incl plasma
used for replacing high Na loss (esp in proximal GI due to NG drainage or vommiting) |
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if you infuse saline whats the ratio of plasma expansion |
ISF: plasma
3-4:1 |
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features of dextrose saline (dextrose 4% + NaCl 0.18%) |
Crystalloid intended for maintenance fluids Iso-osmolar for infusion Majority distributes through total body water compartment (because dextrose is metabolised) Supplies Na+ 31 mmol/L Need to add K+ (eg 20 mmol/L) BEWARE HYPONATRAEMIA - Replace high sodium losses with 0.9% NaCl
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glucose/dextrose 5% features |
Crystalloid intended for maintenance fluids Iso-osmolar for infusion Hypotonic overall effect (because dextrose is metabolised) No Na or K Need to add K (eg 20 mmol/L) BEWARE HYPONATRAEMIA • Not usually suitable as sole fluid for nil by mouth patients |
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why is hypoNa a precaution in dextrose saline and 5% dextrose |
in general they are adding more water to the ECF thus reducing osmolality = hypoNa? |
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dextrose saline and 5% dextrose have similar features ie crystalloid, iso-isomolar, need to add K (eg 20mmol/L) and hypoNa, except for a couple of differences what |
dextrose saline has Na 31mmol/L mostly distributes throughout total body compartments bcuz dextrose is metabolised
5% dextrose has NO Na HyPOtonic overall effect bcuz dextrose is metabolised
nb it doesnt explain but i think the reason why 5% causes cell to swell is becuz theres no Na to help keep water in ECF, plus theres a bit more sugar going into the cell which is not considered osmotically active because of metabolism but surely water will follow via osmosis if theres enough time for it and metabolism is slower |
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crystalloids vs colloids
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Intravascular t1/2 GT for colloid
Haemodynamic stabilisation crys = transient colloid = prolonged
Risk of tissue oedema crys = obvious risk of edema colloid = insig
Risk of anaphylaxis crys=nil colloid=low-mod
Cost crys = inexpensive colloid = expensive
Required infusion volume crys = large colloid = mod
Enhancement of capillary perfusion crys=poor colloid=good
Plasma colloid osmotic pressure
crys=reduced colloid=maintained |
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crystalloids vs colloids - which has a longer half life and is more hemodynamically stable |
colloids |
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crystalloids vs colloids - which requires a larger required infusion volume |
crystalloid |
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crystalloids vs colloids - which has the greatest risk of tissue edema |
crystalloid |
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crystalloids vs colloids - which enhances capillary perfusion better |
colloids |
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crystalloids vs colloids - which is assoc. with NO anaphylatic risk |
crystalloid |
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crystalloids vs colloids - which reduces plasma colloid osmotic pressure |
crystalloids do
colloids just maintain it |
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crystalloids vs colloids - whats the most likely reason why crystalloids are generally used clinically |
cheaper than colloids |
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general principles around use of blood transfusions |
Give early in active bleeding Discuss before giving in stable patients Risks may outweigh benefits in fit patients |
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general guidelines for blood
when do you give blood |
usu if Hb LT 70g/L (rarely need it if Hb GT 100g/L)
Level depends on co-morbidities and context eg lower threshold if elderly coronary disease px or active bleeding |
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If px Hb was over 70 but was an elderly px with CAD would you consider a blood transfusion |
yes, remember levels depend on whether px has comorbidities and context which would be lower for an elderly px with CAD |
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scenarion example
Post op hemi-colectomy (70kg male, fit and well) returns to the ward. You must manage his fluid and electrolyte requirements. NBM for at least 24 hours.
what do you need to give the px |
IV fluids - what and how much |
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4 goals to guide how to approach px needing IV fluids |
1. Go see the px - take hx, exam and relevant InV
2. Replace any pre-existing deficits • Hopefully the anaesthetist will have done this, but there are no guarantees
3. Provide maintenance requirements
4. Replace ongoing abnormal losses • Such as wound drains, NG losses |
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4 goals to guide how to approach px needing IV fluids
1. Go see the px - take hx |
• Pre-operative HX? Reasons for fluid depletion (eg bowel obstruction, vomiting)
• Carefully consider pre-op fluid balance chart and anaesthetic record: -Tally known losses vs known fluid administered -?Haemodynamic instability in OR |
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4 goals to guide how to approach px needing IV fluids
1. Go see the px - EXAM |
• Perfusion and colour, temperature, heart rate, blood pressure, JVP, mucus membranes, skin turgor
• Auscultate the lungs
• What is urine output? -Minimum 0.5 ml / kg / hour
• What is drain output?
• Check dressings and bed clothes |
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4 goals to guide how to approach px needing IV fluids
1. Go see the px - InV |
• Was an ABG done at the end of the case or in recovery? • Full blood count • Urea / creatinine • Electrolytes •.....AND CHECK THE RESULTS • Consider a chest X ray |
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4 goals to guide how to approach px needing IV fluids
2. Replace any pre-existing deficits • Hopefully the anaesthetist will have done this, but there are no guarantees |
Indicated by negative peri-op fluid balance, thirst, ↓ skin turgor, dry mucus membranes, ↓ urine output, tachycardia, hypotension, low JVP
If Hb OK & no signs of failure administer balanced electrolyte or colloid fluid challenges • 250 – 500ml over 10 – 20 min • Favourable change in the parameters that indicated a deficit reinforce your diagnosis |
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4 goals to guide how to approach px needing IV fluids
3. Provide maintenance requirements |
Calculate maintenance requirements • “100:50:20 regimen”
Calculate electrolyte requirements • Na 1 mmol/kg/day • K 0.5 mmol/kg/day
Provide as a basal infusion • K sometimes not started in first 24 hours |
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4 goals to guide how to approach px needing IV fluids
4. Replace ongoing abnormal losses
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* Measure fluid losses in drains and replace with appropriate fluid |
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Reassessment and monitoring - of px needing IV fluids |
Give nurses parameters for heart rate, blood pressure and urine output • Mandate review if not met
Consider daily FBC, creatinine, and electrolyte measurements
Seek advice from senior colleague if concerned |
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Cardiac, renal and liver failure - approach with complications despite IV fluids |
Still must resuscitate if deficits exist
Maintenance volumes are usually lower and endpoints are less predictable
Monitor more intensively • ICU • Invasive monitoring |
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Mg sulfate indicxns |
hypomagnesaemia; arrhythmias; constipation; paste for boils |
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Barriers in access to and management of diabetes for Māori |
evidence that ethnic inequalities in access to and quality of care may play a role
lower rates of screening and early dx despite free blood tests - 80% for NZEuro, 35% for Maori
Lack of community and national prevention of DM
root causes below need to be eliminated to eliminate barriers
nb Low socioeconomic status, stress, and racism are associated with the development of Type 2 diabetes |
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Barriers in access to and management of diabetes for Māori - summary |
ensure primary prevention and early detection of diabetes in Māori. Secondly, regional and local services could undertake analyses of access and quality issues in their service delivery to Māori, develop strategies to improve service delivery, and then monitor the effectiveness of those changes. Broader, contextual issues including structural barriers and socioeconomic barriers must also be addressed |
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Epidemiology of type 1 diabetes mellitus, diabetic ketoacidosis |
t1dm = 5-10% of all diabetic pxs
more common in europeans |
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in some pxs with t1dm have no evidence of autoimmune destruction of pancreatic beta cells - whats this called |
idiopathic DM |
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what are the antibodies you look for in t1dm |
islet cell and islet antigen 2 (IA2) antibodies
GAD antibody (glutamic acid decarboxylase antibody) |
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epidemiology of dka |
around 16% of kids in finland and sweden presented with new onset dka
mostly in t1dm
nb dka and HNKS represent 2 extremes in the spectrum of decompensated dm |
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HNKS epidemiology |
33% pxs with hyperglycemic crisis present with a mixed picture of dka and hnks
incidence and prev. unknown - may be less than 1% for diabetes related hosp. admissions
mortality rates = 5-20% = much higher than dka |
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Implications for type I diabetes mellitus in certain occupations including commercial driving |
Class 1 or class 6 licence and/or a D, F, R, T or W endorsement fit to drive (ie can drive car, tractor, moped/all terrain vehicle, campervan, motorcycle)
Class 2, 3, 4 or 5 licence and/or a P, V, I or O endorsement Generally considered unfit to drive (ie trucks etc) |
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inability to detect developing hypoglycemia increases the risk of crashing for a diabetic patient by how much |
20 x |
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