Step 1 - Renal 1

denniskwinn's version from 2015-04-25 16:17


Question Answer
Course of Ureterspass under uterine artery and under ductus deferens (retroperitoneal) - water under the bridge
Total body water weight percentage60% TBW
ECF vs ICF %1/3 ECF
ECF distribution1/4 plasma volume, 3/4 interstitial volume
ICF composition↑K+,↓NaCl [composition of what compartment]
How to measure plasma volumeradiolabeled albumin [measures?]
Extracellular volume measured byinulin
Composition of Glomerular filtration barrier1. Fenestrated capillary endothelium (size barrier) 2. Fused basement membrane with heparan sulfate (negative charge barrier) 3. Epithelial layer consisting of podocyte foot processes

Tubular/plasma concen. along PT

Question Answer
Creatine approx. GFR, slightly↑
Urea mechFiltered freely, Reabsorbed MORE than PAH& Inulin
HCO3Rapidly reabsorbed
Glucose & AARapidly reabsorb.
Na &K+reabsorb =to water
What subs. will be ABOVE the curvePAH, creatine, urea, Inulin, mannitol
What subs. will beBELOW the curveHCO3, Glu& AA, Na& K

Filtration dynamics

Question Answer
Renal clearance(Urine concentration x Urine flow rate) / Plasma concentration of X
Clearance < GFR =net tubular reabsorption
Clearance > GFR =net tubular secretion of X
Clearance = GFR =no net secretion or reabsorption
Normal GFR100mL/min
Effective Renal plasma flow can be estimated using PAH clearance because it is both filtered and actively secreted in the proximal tubule - All PAH entering kidney is excreted - underestimates true RPF by 10%
GFR estimated byCreatinine clearance (slightly overestimates it - b/c moderately secreted)
Filtration FractionNormally 20% - GFR/RPF; Filtered load = GFR x Plasma concentration
Afferent Arteriole controlprostaglandins dilate afferent arteriole (↑RPF, ↑GFR so FF remains constant) - blocked by NSAIDs
Efferent Arteriole controlAngiotensin II constricts efferent arteriole (↓RPF, ↑GFR - FF increases) - blocked by ACE inhibitor
Renal blood flowRenal artery→interlobar artery→interlobular artery→afferent→glomerulus→efferent→vasa recta→interlobular vein→interlobar vein→renal vein
Effects on glomerulus if Afferent arteriole constricts↓RPF, ↓GFR, No change in FF
Effects on glomerulus if Efferent Arteriole constricts [3 things]↓RPF, ↑GFR, ↑FF [effect on glomerulus if what happens?]
Effects on glomerulus with ↑ in plasma protein concentrationNo change in RPF, ↓ in GFR, ↓ FF
Effects on glomerulus if with ↓ in plasma protein concentrationNo change in RPF, ↑ GFR, ↑ FF
Effects on glomerulus if ureter constrictsNo change RPF, ↓ GFR, ↓ FF


Question Answer
Free water clearance definitionAbility to dilute urine. Given urine flow rate, urine osmolarity, and plasma osmolarIty, be able to calculate free water clearance = total urine (V) - water occupied with solute (C osm)
Free water clearance w/ ADH< 0 = retention of free water
Free water clearance without ADH> 0 (excretion of free water)
Free water clearance in isotonic urine= 0 (seen with loop diuretic)
Calculation of filtered loadGFR x Plasma concentration
Calculation of excretion rateVolume of urine x Cocentration in urine
Calculation of Reabsorption Filtered - excreted
Calculation of Secretionexcreted - filtered
Glucosuria thresholdplasma level of 160-200 mg/dL - at 350mg/dL all transporters are fully saturated (Tm)
Amino acid clearanceSodium-dependent transporters in proximal tubule reabsorb amino acids by at least 3 distinct carrier systems, with competitive inhibition within each group - Deficiency of neutral amino acid (Tryptophan) transporter is called Hartnup's disease, results in pellagra.

renal endocrine reg

Question Answer
Juxtaglomerular apparatus (JGA)modified smooth muscle of afferent arteriole and macula densa - secrete renin in response to ↓ renal blood pressure. ↓ Na+ delivery to distal tubule and ↑ sympathetic tone (beta 1)
Macula densaNa+ sensor in DCT
Kidney endocrine functionsEPO, Vitamin D, Renin, Prostaglandins
Erythropoietin released in response to hypoxia from endothelial cells of peritubular capillaries
1,25-(OH)2 vitamin Dproximal tubule cells convert 25-0H vitamin D to 1,25(OH)2 vitamin D, which ↑intestinal reabsorption of both calcium and phosphate. Parathyroid hormone (PTH) acts directly on the kidney and ↑ renal calcium reabsorption and ↓ renal phosphate reabsorption.PTH also acts indirectly stimulating proximal tubule cells to make 1,25-(OH) vitamin D, which ↑ intestinal absorption of both calcium and phosphate.
Reninsecreted by jC cells In response to ↓ renal arterial pressure and ↑ renal sympathetic discharge (Beta 1 effect).
Prostaglandinsparacrine secretion vasodilates the afferent arterioles to ↑ GFR.

tubule sites of action

Question Answer
Early proximal tubulecontains brush border - reabsorbs all of the glucose and amino acids and most of the bicarb, Na, Cl and water. 2. Isotonic absorption 3. Generates and secretes ammonia, which acts as a buffer for secreted H+
PTH action in proximal tubuleinhibits Na+/phosphate cotransport → phosphate excretion
AT II action in proximal tubulestimulates Na+/H+ exchange → ↑ Na+ and H2O reabsorption (permitting contraction alkalosis)
Thick ascending loop of Henleactively reabsorps Na+, K+, Cl- and indirectly induces the paracellular reabsorption of Mg2+ and Ca2+ - impermeable to H2O - makes urine less concentrated as it ascends
Thin descending loop of Henlepassively reabsorbs water via medullary hypertonicity (impermeable to Na) - concentrating segment - make urine hypertonic
Collecting tubulesreabsorb Na+ in exchange for secreting K+ and H+ (regulated by aldosterone)
Aldosterone action on Collecting tubulesleads to insertion of Na+ channel on luminal side
ADH action on collecting tubulesacts at V2 receptors → insertion of aquaporin H2O channels on luminal side
Early distal convoluted tubuleactively reabsorbs Na, Cl, diluting segment - makes urine hypotonic
PTH actions in early distal convoluted tubule↑ Ca/Na exchange →↑ Ca reabsorption
Angiotensin II actions1. Vasoconstriction (receptors on vascular smooth muscle) 2. Constrict efferent arteriole of glomerulus (↑FF, preserve GFR) 3. Promote aldosterone production 4. Promote ADH production 5. ↑ proximal tubule Na/H activity increasing H2O reabsorption 6. Stimulate hypothalamus (thirst) 7. Effects baroreceptor function, limits reflex bradycardia
Aldosterone actions↑ Na channel, Na/K pump insertion in principal cells, enhances K and H excretion (upregulates principal cells K+ channels and intercalated cell H+ channels) this creates favorable Na+ gradient for Na and H2O reabsorption - primarily regulates blood volume (in low-volume state, both ADH and aldosterone act to protect blood volume)
ANPreleased from atria in response to ↑ volume( ↑ atrial pressure) , may act as a check on RAAS, relaxes vascular smooth muscle via cGMP, causing ↑ GFR (↑ Na filtration w/ no reabsorption compensated) , ↓ renin
Potassium shift out of cell (causing hyperkalemia)1. Insulin deficiency (↓ Na+/K+ ATPase) 2. Beta -adrenergic antagonists (↓ Na+/K+ ATPase) 3 Acidosis, severe exercise (K+/H+ exchanger) 4. Hyperosmolarity 5. Digitalis (blocks Na+/K+ ATPase) 6. Cell lysis
K shift into cell (causing hypokalemia) 1. Insulin (↑ Na+/K+ ATPase) 2. B-adrenergic agonists (↑ Na+/K+ ATPase) 3. Alkalosis (K/H exchanger) 4. Hypo-osmolarity

acid base

Question Answer
Metabolic acidosis changes↓ pH, ↓PCO2, ↓↓ HCO3 - hyperventilation as compensation
Metabolic alkalosis changes↑pH, ↑pCO2, ↑↑ HCO3 - hypoventilation as compensation
Respiratory acidosis changes↓pH, ↑↑pCO2, ↑HCO3 - ↑ renal [HCO3] reabsorption
Respiratory alkalosis changes↑pH,↓↓pCO2, ↓HCO3 - ↓ renal [HCO3] reabsorption
Winter’s formulaUsed to calculate respiratory compensation to metabolic acidosis - PCO2 = 1.5(HCO3) + 8 (+/- 2) - - - PCO2 ↑ 0.7mmHg for every ↑ 1 mEq/L HCO3
Diagnosis and causes of Respiratory acidosisarterial pH < 7.4 and pCO2>40mmHg - Hypoventilation: Airway obstruction, Acute lung disease, Chronic lung disease, Opioids, narcotics, sedatives, Weakening of respiratory muscles
Diagnosis of metabolic acidosisarterial pH< 7.4 and PCO2<40mmHg and probably hyperventilation - check anion gap to determine the type
Anion gap calculation Na+ - (Cl- + HCO3) - normal anion gap value (8-12 mEq/L)
↑ anion gap acidosis causesMUDPILES - Methanol (formic acid), Uremia, Diabetic ketoacidosis, Paraldehyde (or Phenformin), Iron tablets or INH, Lactic Acidosis, Ethylene glycol (oxalic acid), Salicylates
Normal anion gap metabolic acidosis causesDiarrhea, Glue Sniffing, Renal tubular acidosis, Hyperchloremia
Respiratory Alkalosis diagnosis and causesarterial pH>7.4, PCO2<40mmHg - Hyperventilation (early high altitude exposure), Aspirin ingestion (early)
Metabolic Alkalosis diagnosis and causesarterial pH>7.4, PCO2>40mmHg - Hypoventilation compensation - Diuretic use, Vomiting, Antacid use, Hyperaldosteronism


Question Answer
Type 1 Renal tubular acidosis-Defect in collecting tubule's ability to excrete H+.
-Impaired H+ secretion because of H+/K+ pump dysnfunction in the intercalated cell. So there is acidemia (metabolic acidosis) with highly alkaline urine
Associated with hypokalemia and risk for calcium kidney stones
Type 2 Renal tubular acidosis-Defect in proximal tubule HCO3- reabsorption .
-One of the causes for proximal RTA is primary HyperPTH.
PTH inhibits Na+/phosphate co-transport in prox convo tubule and causes phosphate excretion
- AssocIated with hypokalemia and hypophosphatemic rickets.
Type 4 Renal tubular acidosisHypoaldosteronismor lack or collecting tubule response to aldosterone →hyperkalemia → inhibition of ammonia excretion in proximal tubule.
-Hyperkalemia raises intracellular pH by exchange with protons, impairing enzymes involved in ammoniagenesis
-Leads to ↓ urine pH due to ↓ buffering capacity.

cast in urine

Question Answer
RBC casts are sign ofglomerulonephritis, ischemia, or malignant hypertension [casts type]
WBC casts are sign of tubuiointerstltiaI inflammation, acute pyelonephritis, transplant rejection.
Presence of casts indicatesthat hematuria/pyuria is of renal origin
Granular ("muddy brown" ) casts indicateacute tubular necrosis [cast type]
Waxy casts indicateadvanced renal disease/CRF [cast type]
Hyaline casts indicatenonspecific [casts]
RBCs, but no casts, in urine indicateBladder cancer, kidney stones [cast type]
WBCs (ie, pyuria), but no casts in urine indicateAcute cystitis

Nephritic syndromes

Question Answer
Nephritic syndrome-An Inflammatory process. when it involves glomeruli, it leads to hematuria and RBC casts in urine. Associated with azotemia, oliguria, HTN,and proteinuria « 3.5 g/day).
Acute poststreptococcal glomerulonephritis LM-Glomeruli enlarged and hypercellular, neutrophils, “lumpy-bumpy" appearance.
Acute poststreptococcal glomerulonephritis EM vs IF?Nephritic, subepithelial immune complex (IC) humps. vs. IF= granular.
Acute poststreptococcal glomerulonephritis notesMost frequently seen in children Peripheral and periorbital edema. Resolves spontaneously but pretty bad in Adults!!!!
Rapidly progressive (crescentic) glomerulonephritis (RPGN) LM and IF-Nephritic , Crescent- shape.
-Crescent consists of fibrin and plasma proteins with glomerular parietal cells, monocytes, and macrophages
These 3 diseases can result in (RPGN) diseasesNephritic
1. Goodpasture’s (type II hypersensitivity Ab against GBM (linear IF)
2. Wegener’s granulomatosis (c-ANCA)
3. Microscopic polyarteritis (p-ANCA)
Goodpastures syndromeNephritic (RPGN) disease, type II hypersensitivity Ab against GBM (linear IF)
Wegener’s granulomatosisNephritic RPGN (c-ANCA)
Microscopic polyarteritisNephritic RPGN (p-ANCA)
1.Subendothelial DNA-anti-DNA ICs - wire looping of capillaries
2. Granular IF
3. MC cause of death in SLE
Berger’s disease (IgA glomerulonephropathy)Nephritic
1. ↑ synthesis of IgA
2. LM and IF - ICs deposit in mesangium
3. Often presents/flares with a URI or acute gastroenteritis
Alport’s syndromeNephritic
1. Mutation in type IV collagen→split basement membrane
2. Nerve disorders, ocular disorders, deafness
3. X-linked , but can also be AR and AD

Nephrotic syndromes

Question Answer
Nephrotic syndrome [presentation]Presents with massive proteinuria (> 3. 5g/day, frothy urine), hyperlipidemia, fatty cast, edema. A/w thromboembolism and ↑ risk of infection (loss of immunoglobulins).
Membranous glomerulonephritis (diffuse membranous glomerulopathy)Nephrotic,
-LM =diffuse capillary and GBM thickening.
-EM ="spike and dome" appearance with subepithelial deposits.
-IF= granular.
-SLE's nephrotic presentation
Membranous glomerulonephritis (diffuse membranous glomerulopathy) cause-"SPIKE AND DOME", SUB-EPI ICs
-Meds: Captopril, NSAIDs, gold, mercury, penicillamine (chelator), probenecid (gout tx)
-Infections: [eg, HBV, Plasmodium, Syphilis],
-Diseases: SLE, Hodgkin's
Minimal change disease (lipoid nephrosis)Nephrotic
- LM - normal glomeruli
- EM - foot process effacement
-Selective loss of ALBUMIN ONLY, not globulins, due to GBM polyanion loss
2. May be triggered by a recent infection or an immune stimulus
3. MC in children.
4. Responds to steroids.
1. LM - congo red stain, apple-green birefringence
2. A/w MM, chronic conditions, TB, RA
Diabetic glomerulonephropathy
and Tx?
1.(NEG) of GBM → ↑ permeability, thickening. NEG of efferent arterioles (hyaline ateriolosclerosis of eff) ↑GFR → mesangial expansion. Type 1>Type 2
2.LM- MESANGIUM, GBM thickening,
-Nodular glomerulosclerosis (Kimmelstiel-Wilson lesion)
1.LM-segmental sclerosis and hyalinosis
2.MC glomerular disease in HIV patients - more severe in HIV patients
Type I MPGNNephrotic 1.
1.SubENDO lCs with granular IF.
2. Type I EM- “tram-track" appearance due to GBM splitting caused by mesangial ingrowth. 3. Can present as nephritic syndrome
4. Usually progresses slowly to CRF
5. Type I is associated with HBV>HCV
Type II MPGN1. Type II= EM-dense deposits.
2. Type II= a/w C3 nephritic factor((means C3 will be used up), autoab binds to C3 Convertase (C3BBB) leading to sustained activation so VERY LOW C3