physiology Flashcards
nephron physiology - thin descending loop of henle
passively reabsorbs H2O via medullary hypertonicity (impermeable to Na), concentrating segment, make urine hypertonic
describe the nephron physiology:
- Early proximal convoluted tubule
Early Proximal Convoluted Tubule (PCT)
- Contains brush border, reabsorbs 65-80% of Na, via the apical membrane process
- cotransport with glucose, coupling Na+, amino acid, phosphate and organic molecules
- countertransport of H+ ions, H+ ion generate via breakdown of carbonid acid produced by hydration of Co2 cateysed by carbonic anhydrase
- shunt: transepithelial flux of Na and H20
- reabsorbs all of glucose, amino acids, most of HCO3-, Na+, Cl-, PO4, K+and H2O.
- isotonic absorption = high water permeability via AQP-1 (aquaporin 1) water channel (not sensitive to hormonal regulations)
PTH inhibits Na+/PO4 cotransport -> PO3 excretion
ATII - stimulates Na/H exchange -> increase Na, H2o, HCo3 reabsorption (permite contraction alkalosis)
nephron physiology - thick ascending loop of Henle
actively reabsorbs Na (25%), K, and CL via triple contrasport on the basolateral cell membrane
K will recirculate across apical membrane to lumen via specific postassium channel (ROMK) to continue supply of K to match Na and Cl
impermeable to water therefore dilution of luminal fluid (urine) as it ascends
reabsorptive shunt where the small +ve transepithelial potential (K back leak) difference in lumen drive cation (Na, K, Ca, Mg) to cross between cells
nephron physiology - early distal convoluted tubule
6% of Na reabsorption via basolateral Na, K ATPase via sodium cholride cotransporter carrier (NCCT)
impermeable to water -> more dilution of urine (urine hypotonic)
no significant transepithelial flux of K, but Ca reabsorb by basolateral sodium calcium exchanger -> low intracellular Ca concentration promote Ca entry from luminal fluid via Ca channel
PTH - increase Ca/Na exchange -> Ca reabsorption
nephron physiology - collecting tubule
Na reabsorption of 2-3% via epithelial channel generate lumen -ve transepithelial potential difference balance by excretion of K and H and abosorption of Cl (regulated by aldosterone)
aldosterone -> acts on minierlocorticoid receptor -> insertiobn of Na channel on luminal side; also act at V2 receptors -> insertion of aquaporin H2O channels on luminal side
Na reabsorption can be inhibited by natriuretic peptide (Eg. ANP in atrial, BNP in brain)
describe the 4 types of renal tubular defects
- fanconi syndrome
reabsorptive defect in PCT, associated with increase excretion of amino acid, glucose, HCO3, Po4 -> metabolic acidosis (proximal renal tubular acidosis)
cause - hereditary defect (wilson disease),, ischemia, nephrotoxins/drugs - Bartter syndrome
defect in thick ascending loop of Henle, autosomal recessive, affects Na/K/Cl cotransporter cotransporter -> hypokalemia, metabolic alkalosis with hypercalciuria - Gitelman syndrome
reabsorptive defect of NaCl in DCT, autosomal recessive, less sevre then bartter syndrome -> hypokalemia, metabolic alkalosis but NO hypercalciuria - Liddle syndrome
increase Na reabsorption in distal and collecting tubules (increase epithelial Na channel activity), autosomal dominant -> HTN, hypokalemia, metaoblic alkalosis, decrease aldosterone
treated with amiloride
describe the renin-angiotensin aldosterone system
stimulation for renin release from kidney are (decrease bp sense by juxtaglomerular cells, decrease Na delivery via macular densa cells, increase sympathetic tone via beta 1 receptors)
renin have convert angiotensinogen (produce by liver) to angiotensin I then ACE (lungs and kidney) -> angiotensin II
angiontensin II will
- act on AT I receptors on vascular smooth muscle -> vasoconstriction -> increase Bp
- constricts efferent arteriole of glomerulus -> increase FF to preserve renal function (GFR) in low volume states (when RBF decrease)
- trigger release of aldosterone in adrenal gland to increase Na channel and Na/K pump insertion in principal cells; enhance K and H excretion (upregulates principal cell K channels and intercalated cell H ATpases) -> creates favorable Na gradient for Na and H2o reabsorption
- triggers ADH (produce by posterior pituitary) -> increase H2O channel insertion in principal cells -> H2o reabsorption
- increase proximal tubule Na/H activity -> Na, HCO3, H2O reabsorption (can permit contraction alkalosis)
- stimulates hypothalamus -> thirst
describe juxtaglomerular apparatus
consist of JG cells (modified smooth muscle of afferent arteriole) and macular densa (NaCl sensor, part of distal convoluted tubule)
JG cells secrete renin in response to decrease renal blood pressure, decrease NaCl delivery to distal tubule and increase sympathetic tone (beta 1)
JGA defends GFR via renin-angiotensin-aldosterone system
beta blockers can decrease Bp by inhibiting beta 1 receptors of JGA causing decrease renin release
describe kidney endocrine functions (4)
- erythropoietin - released by interstitial cells in peri tubular capillary bed in response to hypoxia
- 1,25(OH)2 vitamin D - proximal tubule cells convert 25 OH vit D -> 1-25 (OH)2 vitamin D (active form) via PTH (calcium homeostasis)
- renin production (JG apparatus) - secreted by JG cells in response to decrease renal arterial pressure and increase renal sympathetic discharge (beta 1 effect)
- Prostaglandins - paracrine secretion vasodilates the afferent arterioles to increase JBF
(NSAIDs block renal -protective prostaglandin synthesis -> constriction of afferent arteriole and decrease GFR -> acute renal failure)
Hormones acting on kidney, describe their effect: ATII ANP PTH Aldosterone ADH
ATII - synthesis in response to decrease bp, cause efferent arteriole constriction -> increase GFR and FF but with compensatory Na reabsorption in proximal and distal nephron.
net effect = preservation of renal function in low volume state (increase FF) with simultaneous Na reabsorption (both proximal and distal) to maintain circulating volume
PTH (parathyroid hormone) - secrete in response to decrease plasma [Ca] or increase plasma [Po4] or decrease plasma 1,250OH vitamin D -> cause increase Ca reabsorption (DCT), decrease PO4 reabsorption (PCT), increase 1,25 OH vitamin D production (increase Ca and Po4 absorption from gut via vitamin D) (act on proximal tubule and distal tubules)
ANP (atrial natriuretic peptide) - secreted in reponse to increase atrial pressure causes increase GFR and increase Na filtration with no compensatory Na reabsorption in distal nephron (net effect: Na loss and volume loss) (act on afferent arteriole and distal tubule)
aldosterone - secreted in response to decrease blood volume (via ATII) and increase plasma [K] causes increase Na reabsorption, increase K secretion and increase H secretion (act on collecting tubule)
ADH (vasopressin) - secreted in response to increase plasma osmolarity and decrease blood volume, binds to receptors on principal cells cause increase # of water channels and increase H2O reabsorption (act on collecting tubules)
what is hypokalemia?
- approach in emergency
- causes
- signs and symptoms
- management
definition of hypokalemia = serum [K+] < 3.5 mEq/L
approach to hypokalemia in emergency
- ECG!! (if life threatening, tx immediately)
- rule out transcellular shift of K+
- assess dietary K+ intake, possible cause?
- 24hr K+ excretion/ spot urine K and urine creatinine (cal urine K+/Cr ratio, normal approx 4)
- TTKG (transtubular potassium gradient) - Uk/Pk (Uosm/ Posm)
- renal K+ loss, check Bp, acid base status
- assess plasma renin, aldosterone levels, serum [Mg]
Possible causes:
1. decrease intake
-limited dietary intake, clay ingestion
2. increased losses - true hematuria (hemoglobin - hemolysis)
- GL losses (diarrhea, laxatives, villous adenoma)
- Renal losses - check BP
if hypo/ normotensive, check acid base -> acidemic (DKA, RTA), Variable (Hypo Mg/ vomiting), alkalemic (diuretics - furosemide, hydrochlorothiazide)/ inherited renal tubular lesions (bartter and gitelmans)
if HTN, 1st/ 2nd degree hyperaldosteronism (1st = conn’s syndrome), 2 = renovascular disease, renin tumour), non-aldosterone mineralcorticoid (cushing, exogenous)
3. redistribution into cells
signs and symptoms
- asymptomatic if mild (3-3.5)
- nausea, vomit, fatigue, *generalized weakness, myalgia, muscle cramps, constipation
- severe: arrhythmias, muscle necrosis, paralysis -> resp impairment (rare)
- ECG!!!!!!!!!!!!
u waves**, flaten/ inverted T waves, arrhythmias, depress ST, prolong QT
severe: PR prolong, wide QRS, arrhythmias, increase digitalis toxicity
management:
- tx underlying cause, if urine output and renal function impair must be careful when correcting!
- risk of hyperkalemia with K replacement
- esp elderly, diabetics, decrease renal function patient
- excessive K replacement -> transcellular shift -> hypokalemia
- true K deficit, potassium repletion via oral (food, tablets, KCL liquid)/ IV (KCL + saline, NO dextrose -> hypokalemia from insulin release)
- K sparing diuretics like triameterene, spironolactone, amiloride
restore Mg if needed
Describe hyperkalemia
- approach
- cause
- signs and symptoms
- tx
definition = [K] > 5 mEq/L
approach
- emergency -> ECG*, if life threaten treat!
- rule out factitiou hyperkalemia (common cause) -> repeat blood test
- hold exogenous K (PO and IV) and any K retain medications
- assess potential cause of transcellular shift
- estimate GFR and TTKG
cause
- facitious (sample hemolysis - common, sample take from from vein where IV KCl running, prolong turniquet)
- increase intake (diet, KCl tablet, IV KCl, Salt subsitute)
- cellular release (intracellular hemolysis, rhabdomyolyis, hyperosmolar states, metabolic acidosis, tumour lysis sydrome, drugs like beta blockers, digitalise overdose (blocks Na/K atpase), succinylcholine)
- decrease excretion (renal failure, low effective circulating vol, nsaids in renal insufficeincy)
signs and symptoms
- asymptomatic but develop nausea, palpitations, muscle weakness, muscle stiffness, paresthesias, areflexia, ascending paralysis, hypoventilation
- impaired renal ammoniagensis and metabolic acidosis
- ECG changes* and cardiotoxicity
Peaked and narrow T waves, decreased amplitude and eventual loss of P waves, prolong PR interval, widen QRS -> merge T wave (sine wave pattern), AV block, ventriuclar fibrillation, asystole
treatment (SEE BIG K DROP)
- see (caclium gluconate), BIG (beta agonist, bicarb, insulin, glucose), K (kayexalate), drop (diuretics, dialysis)
bascially to protect heart, shift K into cells by regular insulin, NaHCO3, Beta 2 agoinst (ventolin), enhance K removal from body via urine (prefered by frusemide, fludrocoritsone), via GIT (cation exchange resins like kayexalate by binding to Na in exchange for K)
dialysis in renal failure or life threatening and unresponsive to tx
normal ph level?
normal Co2 level
normal HCO3 level
Ph 7.35-7.45
Co2 35-45
Hco3 22-26
O2 80-100
- ph < 7.40 + HCO3 < 24 =
- ph < 7.40 + pCO2 > 40
- ph > 7.40 + HCO3 > 24
- ph > 7.40 + CO2 < 40
- metabolic acidosis (decrease HCo3 = decrease PCo2)
- respiratory acidosis (acute: increase 10 Pco2 = increase 1 HCO3) (chronic: increase 10 PCo2 = increase 3 hco3)
- metabolic alkalosis (increase 10 hco3 = increase 5-7 pco2)
- respiratory alkalosis (acute: decrease 10 pco2 = decrease 2 hco3) (chronic: decrease 10 PCo2 = decrease 5 HCO3)
cause of anion gap increased in metabolic acidosis
MUDPILES methanol uremia diabetic/ alcholic/ starvation ketoacidosis paraldehyde (propylene glycol) iron talbets/ INH / isopropyl alcohol ethylene glycol (oxalic acid) salicylates (late)
