Nephrology Flashcards
GFR
- GFR: rate of filtration across the glomerular capillaries into the Bowman’s space
- The sum of the filtration rates of all functioning nephron
- 4 variables: 1) Plasma Flow, 2) Glomerulus Hydraulic Pressure, 3) Glomerulus Osmotic Pressure 4) Ultrafiltration Coefficient
- GFR = Kf x NFP = (K x SA) (ΔP - Δπ)
(Ultrafiltration Coefficient x Net Filtration Pressure) or
(Permeability x Surface Area) (Net Hydraulic Pressure - Net Osmotic Pressure) - Measured based upon clearance (separate card)
- Normal = 80-120 ml/min/l.73m2
Autoregulation of renal blood flow
- Normally: myogenic control (smooth muscle)
- Disease/ hypovolemia: sympathetic NS, RAS, prostaglandin
One of the first signs of kidney damage…
Loss of counter-current mechanism, pelvis can’t become as concentrated, urine isn’t as concentrated
Clearance
- The volume of plasma from which a substance is completely cleared by the kidneys per unit time
- Ideal with inulin, but we use creatinine bc endogenous + formed from muscles at a ~constant rate
- Cr limitations: overestimates due to some secretion, big drop in GFR needed before Cr change, dec muscle mass.
Methods of Calculating
- GFR = C(Cr) = Urine [Cr] (mmol/L) x Volume (L)
Plasma [Cr] (mmol/L) x Time (min)
- C(Cr) via Cockroft-Gault: (140-age) x (weight) x 0.85 if female. (Only valid for steady Cr).
- Most accurate estimation = MDRD eqn (Cr, age, gender, African). (*Only valid for steady Cr + mod-severe CKD)
- Radionuclide kidney clearance = gold std for healthy ppl or AKI
- Normal = 80-120 ml/min/l.73m2
Fraction Excretion (FE)
- Fraction of filtered mass Y that is excreted
- FE(Y) = Uy x PCr x 100
Py x UCr - FE(NA) used for
RAAS Regulation
- Angiotensinogen (liver, into circ)
- Renin (juxtaglomerular cells, kidney)
- AI
- ACE (pulmonary vascular endo)
- AII
- Final effect: vasoconstriction, inc thirst, inc aldosterone (adrenal cortex to DCT)
- Aldosterone - inc Na reabsorption + K secretion - inc BP
*RAS only has an effect in Na/ volume depleted ppl, otherwise normally just myogenic control.
Stimulants of RAS
- Low renal arterial pressure via baroreceptors
- Sympathetics (B1 stimulation of JG cells)
- Low solute (ie Na, Cl) delivered to the macula densa
- PGs (which are in turn stimulated by AII, think +ve FB)
- Low [K]
- Note: high aldosterone inhibits RAS (think -ve FB)
Inhibitors of RAS
- B-adrenergic blocker - JG cells can’t stimulate renin
- Renin inhibitor
- ACE-I
- ARB - AII receptor blocker
Anti-Diuretic Hormone (ADH)
- Hormone from hypothalamus/ post pit –> acts in the distal collecting tubule to inc H2O reabsorption via aquaporins and [ ] the urine.
Stimulants
- Dec circulating blood volume
- Hyperosmolarity
- But note, osmoreceptors are more sensitive to, but baroreceptors are more potent (ex: hypovolemia + hypo-osmolarity = inc ADH)
Transport Max vs Threshold
- Threshold: when one individual tubule is at max reabsorption or when some transporters have been overwhelmed, and the substance begins to appear in the urine
- Transport Maximum: when all tubule thresholds are reached, no more reabsorption, and substance is linearly excreted with amount of filtration
- Ex: start peeing out glucose when blood sugar is ~12-15 mmol/ L –> renal plasma threshold for glc
- Substances that are highly useful and substances that have low use both have higher TMs to be able to be reabsorbed and secreted more, respectively.
Dialysis
- Home > hospital for prognosis, cost, lifestyle, everything
Indications: AEIOU
- A - acidosis/ anemia
- E - electrolyte disturbances (K), elevated BUN, encephalopathy
- I - intoxications
- O - overload
- U - uremia
1) Home Peritoneal Dialysis
- Best for maintaining residual kidney function, but this is lost for 50% of ppl at ~2 yrs post-PD, so they have to switch to usually home hemo. (But other 50% can go on longer-term)
- Simple + short training
- Dialasate provided to anywhere in Cnda
- Cost:
2) Home Hemodialysis
- Sewage capacity + water supply needed
- Longer training (6-8 wks)
- Cost:
3) Hospital Hemodialysis
- Burden on lifestyle + health care system
- Cost:
ESRD Staging
1: Kidney damage with N GFR, >=90
2: Mild dec GFR, 60-89
3: Moderately dec GFR, 30-59
4: Severely dec GFR, 15-29
5: Kidney failure, <15 (70-80% will need dialysis)
3 Ways the Kidney Deals with Acid (Shut these off for Base)
- Bicarb reabsorption/ regeneration
- 90% of filtered bicarb reabsorbed in the PCT (via Na-H exchanger + carbonic anhydrase) + 10% similarly reabsorbed in distal nephron - Titratable Acids
- PO4 and SO4 buffers trap free H in the CT and become titratable acids that can be excreted via urine.
- For every 1 mmol of H excreted, 1 HCO3 is regenerated
- But, this method is limited by the amount of titratable acids that can be formed, so need ammonia - Ammonia* (main way)
- Glutamine → NH4 + HCO3 in the PCT. (Glutamine breakdown increases when inc acidity, but takes hrs-days)
- NH4 flows through to the loop where it is reabsorbed and becomes NH3 + H
- NH3 can cut across and diffuse into the CT, where it traps another H, and is excreted as NH4 in urine
Note: all these methods with buffers work better than excreting free H bc otherwise the urine would be too acidic. (So UNH4 is more accurate than UpH for assessing the kidney’s response to acidity)
Anion Gap (AG) (Metabolic Acidosis)
AG = Na - (Cl + HCO3)
- Normal = 8-12
Used to further differentiate Met Acidosis
1) Increased AG
- “MUDPILES” - methanol, uremia, diabetic ketoacidosis, paraldehyde, isoniazid/ iron, lactic acidosis, ethylene glycol, salicylate. (And toulene in MB)
- Note: quick way to r/o alcohols = osmolal gap (diff bw measured + calculated)
2) Normal AG (most to least common)
- GI loss of HCO3: losing too much HCO3 (ie diarrhea) for ammoniagenesis to compensate
- RTAs (separate card)
- H+ intake
Renal Tubular Acidosis (RTA) (Metabolic Acidosis)
Type 1 RTA - Classical Distal (most common)
- Issues in distal tubule - impaired H+ generation in the cells, inability to secrete H+, or back-leak of secreted H+ back into tubular cells –> dec ammoniagenesis/ UNH4 –> urine can never be maximally acidified (>5.5 as opposed to as low as 4.5)
- Can get bad hypokalemia from Na absorption exchanging with K instead of H
- Etiology: idiopathic, hereditary, 2° to drugs and CKD.
Type 2 RTA - Proximal (v rare)
- Issue in the PCT - Tmax HCO3 is abnormally low –> less reabsorption –> HCO3 spills into the urine much sooner.
- Can get hypokalemia for same reason as type 1
- Etiology: idiopathic, familial, 2° to drugs (eg. acetazolamide – CA inhibitor), disease affecting PCT
Type 4 RTA - Hyperkalemic Distal
- Issue with aldosterone - deficiency (dec renin or dec aldosterone) or resistance - or combo
- Dec aldosterone –> dec Na reabsorbed –> dec K + H secreted –> hyperkalemia –> dec ammoniagenesis –> acidosis
Dx
- Check serum K –> 1 + 2 vs 4
- Test UNH4 for type 1 (most common) via urine AG or urine osmolar gap (separate cards)
Urinary Anion Gap (UAG) - NOT useful/ practical
UAG: [Na + K] - [Cl]
- Normal = ~40
Could differentiate RTAs..
- Appropriate response to acid: Cl is dragged out with every NH4, so if inc NH4 excretion Cl should also be inc –> -ve UAG
- Inappropriate response: +UAG/ not -ve enough
BUT, not practically used bc confounding anions may be in the urine, dragging along Na + K –> affects eqn
Urinary Osmolar Gap
Urine Osmo = 2 (Na + K + NH4) + Urea + Glucose
- Multiply by 2 to account for the anions
- Can solve for NH4 to check if appropriate ammoniogenesis is occurring with acid.
