Exam 3 review Flashcards
List the segments of the nephron
Glomerulus (renal corpuscle), Proximal convolute tubule (PCT), Loop of henle, Distal convoluted tubule, Collecting Tubule and Collecting duct
Glomerulus (renal corpuscle)
Glomerulus (renal corpuscle): Filters blood plasma to form the initial filtrate which will become urine. It allows SMALL substances such as water, electrolytes, glucose and waste products to pass into bowmans capsule. Has a network of capillaries surrounding capsule.
Proximal convolute tubule (PCT)
Reabsorbs 80% of the water, sodium, chloride, bicarbonate, glucose and amino acids. Responsible for secreting certain substances like hydrogen ions, drugs, and ammonia into filtrate.
Target for diuretics: carbonic anhydrase inhibitors and osmotic diuretics.
CAI: block NaHCO3 reabsorption, affects pH.
Osmotic diuretics: Increase osmolality, prevents water reabsorption
Loop of henle
descending limb: permeable to water, allowing water to be reabsorbed.
Thick ascending limb: imperable to water but actively reabsorbs potassium, sodium, chloride via the NKCC2 transporter. This creates a driving force to reabsorb calcium and magnesium.
Diuretics: Furosemide (inhibits NaCl reabsorption in the thick ascending limb, leading to a decrease in sodium reabsorption and causing water/electrolyte loss.
Distal convoluted tubule
involved in sodium and chloride reabsorption through the NCC transporter. Reabsorbs calcium under influence of parathyroid hormone.
Diuretic: Thiazides (inhibit NaCl transport and have a mild effect on carbonic anhydrase activity)
Collecting Tubule and Collecting duct
These are critical sites for regulation of water and sodium reabsorption. Collecting tubule is important for potassium secretion, collecting duct is where ADH acts to increase water reabsorption, concentrating urine.
Diuretics: Potassium-sparing such as spironolactone (block aldosterone receptors or inhibit sodium channels to prevent potassium loss)
Also ADH antagonists such as conivaptan (reduce water reabsorption by blocking ADH receptors)
Define where the following are occurring: filtration, reabsorption, secretion.
Filtration: glomerulus within bowmans capsule, which is a network of capillaries. Filters SMALL solutes.
Reabsorption: Primarily PCT, also occurs in loop of henle, DCT, collecting duct. Essential electrolytes and water are reabsorbed back into blood stream.
Secretion: Primaily PCT, also DCT. Involves active transport of substances such as potassium and certain drugs, from bloodstream into tubular fluid of nephron. Crucial for regulating pH balance and removing substances that were not previously filtered at glomerulus.
Describe the location and function of the macula densa and juxtaglomerular apparatus.
Macula densa is in the DCT, specifically where the DCT is in close proximity with the glomerulus. It monitors osmolality and volume of fluid within DCT, and will communicate with the juxtaglomerular cells to adjust blood flow and concentration.
Juxtaglomerular apparatus: at the vascular pole of renal corpuscle, where the afferent arteriole and DCT come into close contact. It regulates blood pressure and GFR through renin secretion and adjusting blood flow.
Define how the kidneys regulate GFR.
They regulate their own blood flow to maintain a consistent GFR despite systemic blood pressure
Renal autoregulation: Macula densa senses osmolality and fluid volume, and if it detects high sodium levels or increased fluid flow (high GFR), it signals juxtaglomerular cells to decrease Nitric Oxide, causing vasoconstriction of afferent arteriole, reducing bloodflow, thus lowering GFR.
Juxtaglomerular feedback mechanism: detects a decrease in sodium or reduced fluid flow (low GFR), signals JG cells to relax by increasing NO, allowing more blood flow. Also release renin, promoting water reabsorption.
Neural regulation: SNS releases norepi/epi, causing vasoconstriction and reducing GFR to conserve fluid and maintain BP.
Hormonal: renin release by JG cells, stimulating RAAS and increasing water reabsorption.
Describe the function of NHE3 and carbonic anhydrase in sodium and bicarb reabsorption.
NHE3: Sodium-Hydrogen exhanger 3, found in PCT, facilitates exchange of Na+ and H+. Na+ is transported into cell in exchange for H+ into the lumen. H+ combines with Bicarb to form Carbonic Acid (H2CO3)
Carbonic Anhydrase (CA): in PCT, catalyzes conversion of carbonic acid into water and CO2. CO2 diffuses freely and reforms Carbonic acid, which then dissociates back to BIcarb and H+. Then, Bicarb is reabsorbed into blood stream while H+ ions are recycled back into lumen via NHE3
Summary: NHE3 allows sodium to be reabsorbed while simultaneously secreting hydrogen ions. CA facilitates rapid conversion and recycling of CO2 and bicarb, enabling efficient reabsorption of both sodium and bicarbonate into bloodstream.
Essential for maintaining acid-base balance and electrolyte homeostasis in body.
CA inhibitors are old school diuretics no longer used d/t their effects on pH
Describe how the osmolality of the kidney medulla affects water movement.
Creates a gradient of increasing osmolality as it dips from the cortex into the medulla. Deeper into the medulla, higher the osmolality (up to 1200mOsm/kg)
The hypertonic environment of the kidney medulla is critical for water reabsorption, and it ensures that water moves out of the nephron when necessary such as during the presence of ADH, allowing kidney to concentrate urine and maintain body fluid balance.
List 5 major types of diuretics and relate them to their sites of action, urinary electrolytes, and main side effects.
Carbonic Anhydrase inhibitors, Loop diuretics, thiaizide diuretics, potassium sparing diuretics, osmotic diuretics
Loop diuretics - sites of action, urinary electrolytes, and main side effects.
-Thick ascending limb of loop of henle
- Increases excretion of Na, Cl, K, mg, and ca
- Hypokalemia, hypomagnesemia, hypocalcemia, and ototoxicity (related to high doses or rapid IV admin)
Carbonic anydrase inhbitors sites of action, urinary electrolytes, and main side effects
-PCT
-Increases excretion of bicarb, sodium, and potassium
-Metabolic acidosis due to loss of bicarb, and hypokalemia
Thiazide diuretics - sites of action, urinary electrolytes, and main side effects.
-DCT
-increased excretion of Na, Cl, K
-Increases reabsorption of Ca
-Hypokalemia, but hypercalcemia, hyperglycemia, hyperuricemia
Potassium sparing diuretics - sites of action, urinary electrolytes, and main side effects.
Collecting tubule and uct
- Increases excretion of Na and retains K+
- Hyperkalemia and endocrine effects (specific to spironolactone
Osmotic diuretics - sites of action, urinary electrolytes, and main side effects.
- PCT and descending loop of henle, collecting duct
- increased excretion of Na, K and water
- Dehydration, electrolyte imbalance could be hypo or hypernatremia, hyperK, and volume expansion (initial extracellular volume expansion, possible causing pulmonary edema
Define “potassium wasting”.
diuretics causing the kidneys to excrete an excessive amount of K+, primarily occuring in collecting tubule and collecting duct. Inhibit sodium reabsorption earlier in nephron, resulting in increased sodium delivery to collecting tubule and enhanced K secretion. Also driven by aldosterone.
Loop and thiazide diuretics - Furosemide and Thiazide
Explain the mechanism of potassium and bicarb wasting in the collecting tubule following specific diuretic administration.
potassium wasting: triggered by increased Na delivery to collecting tubule due to upstream diuretics, results in enhanced potassium secretion to maintain electrolyte balance.
Bicarb wasting: caused by carbonic anhydrase inhibitors reducing bicarb reabsorption upstream, leading to excretion downstream in the collecting tubule
Describe 2 drugs that reduce potassium loss during sodium diuresis.
potassium sparing diuretic: spironolactone and amiloride
Spironolactone is an aldosterone antagonist, reducing activity of epithelial sodium channel.
Amiloride: directly inhibits epithelial sodium channels, which results in blocked sodium reabsorption, and now potassium secretion isn’t being driven into urine by sodium reabsorption.
Compare the effects of mannitol to other diuretics and list its uses and potential side effects.
Osmotic diuretic, preventing water reabsorption, increasing urine volume.
uses: reduction of intracranial pressure, intraocular pressure, promotion of reneal excretion of toxins (rhabdo or drug overdose), management of AKI by maintaining urine flow.
side effects: dehydration, electrolyte imbalances, crystallization
List the major applications and the toxicities of potassium-sparing diuretics.
preventing hypokalemia, and treating aldosteronism, as well as hypertension.
toxicities: hyperK, endocrine effects, metabolic acidosis from H+ buildup
Thiazides major applications and toxicities
Hypertension (reduce blood volume and relax vessel walls), edema in CHF, prevent calcium stones, nephrogenic Diabetes insipidus (REDUCES URINE OUTPUT by increasing sodium and water reabsorption), Heart failure
-Toxicities: hypoK, hypercalcemia, hyperglycemia, hyperuricemia, hyponatremia.
Combine loop with thiazides -> huge movement of NaCl to urine
Acetazolamide major applications and toxicities
Carbonic anhydrase inhibitor:
Glaucoma (reduces production of aqueous humor)
Acute mountain sickness by promoting metabolic acidosis. Metabolic alkalosis (same reason as mountain sickness), Epilepsy, edema.
Toxicities: metabolic acidosis, hypoK, renal stones, drowsiness.
Loop diuretics major applications and toxicities
Most powerful, manages severe edema such as with CHF, cirrhosis, nephrotic syndrome. Acute pulmonary edema, hypertension, hypercalcemia, and ARF.
Toxicities: hypoK, hypomagnesemia, hypocalcemia, ototoxicity. Avoid in pt’s with sulfa allergies.
Discuss the use of diuretics in patients with diabetes insipidus
Di is the kidneys inability to concentrate urine, insufficient ADH.
-Thiazide diuretics are used for nephrogenic DI, they reduce urine output by decreasing the GFR and enhancing sodium and water reabsorption in the proximal tubule. By reducing the delivery of sodium and water to distal nephron and collecting duct, helps decrease overall volume of dilute urine.
List the symptoms and factors involved in airway obstruction in asthma
Symptoms: wheezing, breathlessness, chest tightness, coughing
Factors:
- airway inflammation involving inflammatory cells like WBCs, epithelial cells
- Increased airway responsiveness, sensitivity of trachea and bronchi
- Contraction of smooth muscle (driven by histamines and leukotrines)
- Mucosal thickening
- Mucus hypersecretion
List the symptoms and factors involved in airway obstruction in croup
Seal-like barking cough, rhinorrhea, sore throat, fever
Factors: typically occurs due to acute laryngotracheobronchitis, often caused by viral infections (alot in children)
-Leads to airway narrowing and increased mucus production
List the symptoms and factors involved in airway obstruction in COPD
Dyspnea, wheezing, chronic productive cough, Fatigue and excercise intolerance.
Factors: Chronic bronchitis, emphysema (permanent enlargement of gas-exchange airways)
List the symptoms and factors involved in airway obstruction in bronchitis
Chronic productive cough, dyspnea, wheezing, fatigue
Factors: increased mucus (inhaled irritants), inflammation of bronchial tubes, enlargement of mucus glands, loss of ciliary function
List the symptoms and factors involved in airway obstruction in emphysema.
dyspnea, reduced exercise tolerance, wheezing, fatigue, barrel chest
Factors: destroyed alveolar walls, loss of elastic recoil, airway collapse, increased airway resistance.
Describe airway function tests.
FEV1: forced expiratory volume in 1 second, monitors conditions like asthma and COPD
PEF: peak expiratory flow, measures highest flow rate achieved during forceful expiration.
Describe the immune response to allergens as it pertains to the following cells: dendritic cells, T cells, B cells, plasma cells, mast cells, neutrophils, and eosinophils.
-Dendritic cells initiate immune response
-T cells are activated by dendritic cells, release cytokines. attract B cells and eosinophils
- B cells produce antibodies
- Plasma cells are specialized B cells
- Mast cells release mediators that cause inflammation
- Neutrophils are first responders in acute inflammation
-Eosinophils are key inflammatory cells especially in asthma, late phase response.
List the mediators released in the early and late stages of asthma and their effects.
Early:
-histamines (cause smooth muscle contraction and mucosal edema/excretion.
-Tryptase, leukotrienes (prolong bronchospasm, hypersecretion), prostaglandins (induce bronchoconstriction).
Late: cytokines, eosinophils, TNF-alpha
Describe the main pharmacokinetic features, and list the adverse effects of carbamazepine, phenytoin, lacosamide, phenobarbital, ethosuximide, and valproic acid.
Phenytoin: oldest drug. Alters sodium, potassium and calcium conductance, likely also affects gaba and glutamate. Toxic at higher doses. 10% of doses are free-bound. -Toxicity: Gingival hyperplasia, hirsutism, coarsening of facial features, dose related, nystagmus, loss of extra ocular pursuit of movement, diplopia, ataxia, sedation.
Carbamazepine: TCA!!, tegretol. Similar to phenytoin, blocks Na+ channels at therapeutic concentrations. For focal seizures, can be used with phenytoin, effective for trigeminal neuralgia (nerve on side of face that can cause burning sensation) and bipolar disorder. peaks at 6-8 hours, not a very long half life. 70% bound to plasma, doesn’t displace other drugs but it does compete for binding sites. After 1 dose, its half life is 36 hours, but during continuous therapy its 20 hours due to metabolism adjustment/autoinducer of itself.
Lacosamide: focal seizures, blocks sodium channels. Near equal efficacy at different doses, 200,400,600… Toxicity: not as toxic as phenytoin, dizziness, nausea, HA, diplopia, minimal drug interactions.
Phenobarbital: one of the safest. Don’t know its exact MOA, but likely enhances GABA and decreases excitatory transmission, may suppress abnormal neurons. Drug of choice in infants. used for Focal seizures, generalized tonic-clonic.
Not useful for absence, atonic, or infantile spasms and may actually worsen them.
Toxicity: SEDATION MAINLY, overdose (steady gait, slurred speech, confusion, response depression, coma
Ethosuximide: absence seizures, safe and effective.
Inhibits calcium channels. toxicity: Gastric distress, lethargy
Valproic acid: Depakene/depakote
Unknown MOA but it blocks sustained high frequency firing, effects on Na+ currents, increase GABA, and increases K+ conductance.
Used for absence seizures, some types of myoclonic, gen tonic-clonic, bipolar, migraine prophylaxis.
IT DISPLACES PHENYTOIN OFF ALBUMIN AND CAN INCREASE TOXIC LEVELS OF PHENYTOIN.
Toxicity: all gi - N/V, pain, heartburn
