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.
Urinary Chloride (Metabolic Alkalosis)
1) Chloride Responsive - Low Cl (20 mmol/L)
- High mineralcorticoids (ex: adrenal hyperplasia, Cushing’s): hypertension from inc Na rebasorption from aldosterone. Also inc Na delivery to DCT –> inc K + secretion –> alkalosis
- Current diuretic: losing everything (Na Cl high in urine)
- Bartter or Gitelman syndrome (rare)
Vomiting –> Chloride Responsive Metabolic Alkalosis
- Directly lose ↑ H + Cl and some of K + Na –> Na loss and low Na intake = dec volume –> inc Na reabsorption in PCT, but also HCO3 (bad)
- Some HCO3 passes to DCT and is reabsorbed there with Na instead of Cl with Na (bad again) –> Cl secreted (hence high urine Cl)
- HCO3 also drags Na + K into the urine after reaching its Tmax (bad)
- Also the dec GFR won’t even bring as much bicarb to be filtered (bad).
SO, vicious cycle - the alkalosis limits the hypovolemia correction (bc HCO3 drags Na + H2O), and the hypovolemia limits effective HCO3 excretion (bc dec filtration). filtered). First the met alk is generated, and then maintained bc of the ↓ GFR, ↑ HCO3 reabsorption, and aldosterone causing avid distal Na reabsorption
- End result: hypoCl, hypoK, low urine Cl, and variable Na depending on if HCO3 reached Tmax or not.
- Stop cycle with FLUIDS
Potassium - Electrical Conductance
- K + Ca have opposite effects on electrical conductance. Low serum K = inc conductance, but low serum Ca = dec.
- -> Can treat life-threatening hyperkalemia acutely with Ca
- -> Think of both together when treating
Potassium - Homeostasis
1) Extra-renal shift, ie trans-cellular (mins - 1 hr)
- Epi/ B adrenergic stimulation: inc cell uptake
- Insulin: inc cell uptake
- Aldosterone: inc cell uptake
- Acid base status: met alk (low H) = H out of cells + K in + hypoK, met acid (high H) = H in cells + K out + hyperK in mineral acidosis, but in organic acidosis (ketoacidosis), the ketone just goes with the H instead of need a K exchange.
- Plasma osmolarity: H2O out –> inc ICF [K] –> K moves out of cell (initial hyperK with hyperglycemia)
2) Renal excretion (6-8 hrs - days)
- Depends on intracell K in tubule, aldosterone (inc pumps and lumen permeability to K), electrical gradient, flow rate, dietary K, etc
Potassium - Trans-tubular K Gradient (TTKG)
TTKG = Urine [K] X Plasma Osmolarity
Plasma [K] Urine Osmolarity
- Normal = ~8
- Used to estimate the tubular K content at the end of the CCT
- Requirements: enough Na delivery, aldosterone, and urine osmo > plasma osmo
- Can differentiate transtubular/ transcellular shifts or poor intake (6)
- Hyperkalemia with normal tubular fncn >10
SIADH
Etiology
- S: surgery
- I: intracranial (infection, head injury, CVA)
- A: alveolar (Ca, pus)
- D: drugs (opiates, anti-epileptics, cytotoxics, anti-psychotics)
- H: hormonal (hypothyroid, low corticosteroid level)
S+S
- Euvolemic hypoNa (UOsm >100)
- Spasms, anorexia, disorientation/ psychoses
Dx
- R/o adrenal insufficiency (cortisol), hypothyroid (TSH), meds (carbamazepime, thiazide diuretic, etc) – appropriate reasons for high ADH.
Etiology
- Cancer (lung), intracranial pathology, pulmonary disease, esp disorders that inc intrathoracic P + dec VR to heart –> CXR, CT chest/ brain
Approach to Acid-Base Disorders
HCO3/ CO2 content = 22-26 mmol/L (use 24)
PCO2 = 35-42 mmHg (use 40)
pH = 7.38-7.42 (use 7.4, [H] 40)
AG = 8-12 mmol/L
[H] = 40 –> pH = 7.4. +/- 1nmol H = +/- 0.01 pH in opp direction. So [H] = 35 –> pH = 7.45
1) Lab Error
2) pH (acidic, alkalotic, or normal)
- Find the PCO2 or HCO3 abnormality in the same direction as the pH disturbance –> determines resp or metabolic
- Normal pH + abnormal values = multiple issues –> pick the most abnormal
- If pH isnt given, determine via Henderson eqn
3) Assess adaptive response
- Resp acid: ↑ 1 mmHg PCO2, ↑ HCO3- by 0.4 mmHg
- Resp alk: ↓ 1mmHg PaCO2, ↓ HCO3- by 0.4 mmol/L
- Met acid: ↓ 1 mmol HCO3, ↓ PaCO2 by 1.2 mmHg
- Met alk: ↑ 1 mmol HCO3-, ↑ PaCO2 by 0.6 mmHg
- If not w/i +/- 2, then have an additional disorder
4) Anion Gap (N = 8-12)
- AG = Na - (Cl + HCO3)
- Can narrow ddx for met acid
- Met alk can also be moderately high (12-15)
5) ↓ HCO3 = ↑ AG → simple AG metabolic acidosis
↓ HCO3 > ↑ AG → also have a normal AG metabolic acidosis
↓ HCO3 < ↑ AG → also have a metabolic alkalosis
- Note: the body can handle acidosis much better than alkalosis
Plasma Osmolality
= 2xNa + glc + BUN (“2 Nas on a sticky bun”)
Determined by thirst (hypothalamus, senses changes in plasma osmolality + effective intravascular volume), renal handling of H2O, and ADH.
Diuretics
- Loop Diuretics
- Lasix - Potassium Sparing Diuretics
- Spironolactone - Thiazide Diuretics
- Hydrochlorothiazide
- > One of the most common drugs associated with hypoNa
- > Interferes with diluting segment -> mild intravascular volume depletion -> inc ADH release/ thirst
AKI
Defn: Cr inc >=26.5 umol/L over 48 hrs, inc >= 50%, OR urine output 6hrs.
- Stages = “RIFLE” - risk, injury, failure, loss, ESRD, depending on increasing severity of inc Cr/ dec urine.
- GFR can’t be estimated during AKI -> assume <10mL/min
Prevention
- GFR estimates are more reliable than Cr changes - routinely check it in pts at risk
- Avoid: NSAIDs, contrast, aminoglycoside abx. (If have to use contrast, pre+post saline/ bicarb. If hypovolemic (relying on RAS for GFR), avoid ACE-I/ ARB.
Pre-renal VS Renal vs Post-Renal (separate slides)
CKD
Defn: >=3 mos of GFR proteinuria)
- -> Target BP Target BP 1.5mmol/L), protein 0.6g/kg/day (if stg 4 or 5)
- No: laxatives with Mg or PO4, NSAIDs, COX-2 inhibitors, contrast
- HbA1C <7% to slow progression
Urine Investigations
Dipstick
- pH (tubular disorder), specific gravity, glycosuria (DM, proximal tubular dysfunction)
- Albumin (only protein reliably detected with dipstick. Inc excretion is often the earliest sign of glomerular injury).
- leukocyte esterase/ nitrites -> usually UTI
Microscopic
- Hematuria (>3 rbc/hpf). Can distinguish hemoglobinuria vs myoglobinuria
- Pyuria (>3 leukocytes/hpf) -> UTI, interstitial nephritis
- Eosinophils -> drug-induced interstitial nephritis, RPGN, small vessel vasculitis
- Epi casts -> ATN
- Hyaline casts -> [ ] urine. Granular hyaline casts -> albuminuria, nephritic range proteinuria
24 Hr Urine Collection
- Immunoglobulins (ie Bence-Jones in multiple myeloma)
Proteinuria
- Quantitative measurement: spot protein: Cr > 24 hr urine due to inconvenience/ imprecision. 1st AM samples preferred. 2 positive tests 1-2 wks apart = persistent proteinuria -> further evaluation.
- -> 0.2-2mg -> chronic tubulointerstitial, renovascular, or glomerular disease
- -> >3.5mg -> nephritic range
- Albumin: Cr is often more sensitive bc
- Other: isolated/ transient/ <1g/24 hr may be from fever or ++ exercise. Orthostatic proteinuria (inc standing, N lying)
Nephrotic Syndrome
Etiology
- 1°: minimal change, membranous, focal segmental, membranous nephropathy, amyloidosis
- 2°: DM, dysproteinemia, HIV, hep B, SLE
S+S
- Nephrotic range proteinuria (protein:Cr >3.5mg, dipstick >2+)
- Bland urine sediment (may contain hyaline/ hyaline granular casts, lipids, none-some rbcs)
- Hypoalbuminemia
- Edema
Nephritic Syndrome
Etiology
- Commonly PIGN, IgA nephropathy, membranoproliferative GN. Also SLE
S+S
- Varying amount of proteinuria
- Active urine sediment (may contain granular casts, med-high dysmorphic rbcs, rbc casts)
- Can have renal-dermal syndromes (purpura, necrosis, ulcers, nodules, SLE, ANCA vasculitis, cryoglobinuria, Henoch-S purpura). Or renal-pulmonary syndromes.
AKI - Pre-renal
Etiology/ Pathophys
- Absolute dec in ECF volume (GI loss, hemorrhage)
- OR dec renal blood flow (HF, renal artery stenosis)
- OR altered intra-renal hemodynamics (sepsis, hyperCa, cirrhosis/hepatorenal syndrome, abdo compartment syndrome, drugs - NSAIDs/COX2 inhibitor, ACE-I, ARB)
Labs/ Investigations
- BUN: Cr >15:1, UNa 1.018.
Tx
- NS
- Albumin if v low or pt has portal htn + ascites
- D/C all NSAIDS + diuretics, dec/ D/C ACE-I/ ARB
- Except hepatorenal syndrome has extreme vasoconstriction and won’t respond to intravascular volume repletion
AKI - Renal
Etiology/ Pathophys
- Tubular - ATN (ischemic, nephrotoxic)
- > Most common cause = sepsis
- > Toxins: aminoglycoside, amphotericin B, cisplatin, contrast, cocaine
- OR interstitial - AIN (allergic, NSAID)
- OR glomerulus (glomerulonephritis, thrombotic microangiopathies, atheroembolic disease)
- OR vasculature (vasculitis, microangiopathic hemolytic anemia)
AKI - Post-renal
Etiology/ Pathophys
- Anatomic obstruction (bladder, ureteral)
- OR tubular obstruction (crystals, drugs, proteins)
- > Tumour lysis + chemo (high serum uric acid), myeloma (immunoglobulin light chains), antiviral precipitate (acyclovir, indinavir)
Labs/ Investigations
- # 1 = renal US
- May see micro/macro hematuria, bacteriuria, pyuria, crystal deposition. Or UA may be normal
- Urinary catheter if urinary obstruction
- Retrograde/ antegrade nephrostomy if obstruction above bladder
Azotemia vs Uremia
Azotemia: elevated Cr
Uremia
- Usually at Cr clearance <10mL/min, but higher for some, esp if AKI
- N/V, dec mental status, sz, pericarditis, fatigue, muscle cramps, anorexia, wt loss, itchy, asterixis, pericardial rub
