Clinical Vignettes Flashcards
Presentation of DKA
Polyuria Polydipsia Dehydration Electrolyte imbalances Weight Loss Rapid, deep breathing (Kussmaul respirations) Nausea & Vomiting
How is Diabetes Diagnosed?
HbA1c > 6.5%
Fasting plasma glucose > 126 mg/dL
2 hour plasma glucose tolerance levels > 200 mg/dL
Random plasma glucose > 200 mg/dL in a patient with classic symptoms on hyperglycemia
How is DKA defined?
Hyperglycemia - plasma glucose > 200 mg/dL (normal: 70-120 mg/dL)
Ketonemia and ketonuria (negative, trace, mild, moderate, large)
Metabolic Acidosis
Venous pH < 7.4 and/or HCO3- < 15 mmol/L
(normal pH: 7.28-7.32, normal HCO3-: 3.5-4.5)
Clinical features of Cholera
Watery feces with presence of mucus (up to 1L/hr)
Vomiting
Severe and rapid dehydration (tachycardic, skin tenting)
Pathophysiology of Cholera
Vibrio cholerae secretes cholera toxin (CT); CT-Beta binds to the GM1 ganglioside receptor on the lumenal surface of cells in the small intestine, at which point the alpha subunit is cleaved off and endocytosed; it binds to intracellular Gs-alpha, stimulating adenylyl cyclase to produce cAMP, which activates CFTR to efflux chloride ions, followed by water, into the intestinal lumen.
Mechanism of ORT in Cholera
ORT solutions take advantage of sodium co-transporters in the apical membrane; giving Na along with glucose or AAs drives Na co-transport into the cell through the apical membrane; as Na is transported from the lumen into the cell, Cl- and water follow
Multiple Sclerosis
MS is an auto-immune disease characterized by inappropriate reaction of T-cells and B-cells to myelin in the brain, causing inflammatory demyelination and decreased speed of conduction in the nerves
Clinical Presentation of MS
Fatigue Walking impairment (Ataxic, Spastic) Muscle weakness (foot drop) Loss of Balance Spasticity Cognitive Impairtment Pain
Dalfampridine
Indication: To improve walking speed in patients with MS
Mechanism: K+ channel inhibitor; enhances conduction of action potentials in demyelinated axons
Side effects: Increased neuropathic pain, seizures
Demographics of MS
MS affects nearly 500,000 Americans
Female to Male Risk Ratio - 2.4:1
80% develop MS between 16 and 45 years
Without treatment, 50% require cane within 10 years of onset; 30% will become wheelchair or bed bound
Mechanism of insulin release
Glucose entering the pancreatic beta cell through the GLUT2 transporter undergoes glycolysis, leading to an increase in ATP; this signals the ATP-sensitive K-channel to close, preventing outward leak of K; build-up of intracellular K depolarizes the membrane, activating a voltage-gated Ca channel and leading to Ca influx, which signals exocytosis of insulin-containing secretory granules.
Mechanism of acidosis in DKA
Because pancreatic beta cells are not producing insulin, body cells do not have adequate uptake of glucose to make ATP; they initiate beta oxidation of fatty acids, which generates hydrogen ions and ketone bodies (acetoacetate and betahydroxybutyrate). To compensate for metabolic acidosis, the body increases respiratory volume and rate to eliminate carbon dioxide, driving the bicarbonate buffer reaction toward consumption of excess H+.
Dehydration in DKA
Dehydration occurs as a result of osmotic diuresis secondary to hyperglycemia; in diabetes, blood sugar is so high that it cannot all be reabsorbed in the kidneys; excess glucose is excreted in the urine, along with large volumes of water needed for osmotic balance of the urine
Potassium derangements in DKA
- In response to dehydration, the body conserves sodium in order to create an osmotic force that helps conserve water; the body activates aldosterone, which stimulates an antiport mechanism that takes in sodium at the expense of excreting potassium into the urine
- Acidosis leads to the uptake of H+ ions in exchange for the release of K+ into the ECF (hyperkalemia)
Therefore, patients may present with hyperkalemia despite overall potassium depletion
2 Cause of cerebral edema in DKA
Total body osmolarity increases in DKA due to hyperglycemia and sodium retention secondary to dehydration; therefore, giving fluids that are normally isotonic may actually be hypotonic to this patient, causing movement of water across the BBB via osmosis and swelling of the brain
Giving insulin improves ketoacidosis; decreased H+ in the ECF drives K+ back into cells, which can create an osmotic gradient pulling water into the cells in the brain
Signs and treatment of cerebral edema in DKA
Fixed, dilated pupils (CN III palsy)
Cushing’s triad (hypertension, bradycardia, irregular respirations)
Mental status changes
Treatment: IV mannitol, which raises the effective osmolarity of the blood and pulls water out of the brain in order to decrease swelling
Sodium Channel Blockade in MS
Demyelination produces a proliferation of Na+ channels along axons; increased Na+ entry into the cell may actually reverse the polarity of the Na+/Ca2+ exchanger, leading to an influx of Ca2+ which damages the axon
Na+ channel blockers Phenytoin and Flecainide preserve axons
