Renal Flashcards
Which structure in kidney development functions as an interim kidney for the 1st trimester and later contributes to the male genital system?
Mesonephros
When does the metanephros appear? What two embryonic structures are a part of the metanephros?
First appears in 5th week of gestation
- Uteric bud (from caudal end of mesonephric duct)
- Metanephric mesenchyme - interacts with uteric bud
What arises from the ureteric bud?
What arises from the metanephric mesenchyme?
Which embryonic structure is the last to canalize?
Ureteric bud: gives rise to ureter, pelvises, calyces and collecting ducts
Metanephric mesenchyme: interaction with ureteric bud induces formation of glomerulus through to distal convoluted tubule
Last to canalize (most common site of obsruction) is uretopelvic junction
What congenital defect is due to abnormal interaction between the ureteric bud and metaneprhic mesenchyme?
Multicystic dysplastic kidney (bilateral form often confused for ARPKD)
Ureters pass under the ________ in females and the __________ in males
Uterine artery; Ductus deferens
Total body water is __% of body weight
ICF is __% of body weight and __ of total body water
Interstitial volume is __% of body weight and __ of extracellular fluid
Total body water is 60% of body weight
ICF is 40% of body weight and 2/3 of total body water
Interstitial volume is 15% of body weight and 3/4 of extracellular fluid
Extracellular volume is measured by ________
inulin
How is renal clearance calculated? What does it mean if clearance of a substance is < than GFR?
Cx = UxV/Px where U = urine concentration, V = urine flow rate and P = plasma concentration
If Cx < GFR then there is a net tubular reabsorption of X
How is effective renal plasma flow estimated? Why is this used?
Estimated using para-aminohippuric acid (PAH) clearance because it is both filtered and actively secreted in the proximal tubule (all PAH entering the kidney is excreted)
How is the ERPF (effective renal plasma flow) calculated? How is this corrected to represent renal blood flow?
ERPF = UPAHxV/PPAH = CPAH
RBF = RPF/(1-Hct)
What is the normal filtration fraction?
How is filtered load calculated?
What is the equation for filtration fraction?
Normal FF = 20%
Filtered load (mg/min) = GFR (mL/min) x plasma concentration
FF = GFR/RPF
How is hartnup disease inherited?
What is deficient and where?
What symptoms are present?
- Autosomal recessive
- Deficiency of neutral amino acid transporters in proximal renal tubular cells and on enterocytes
- Pellagra like symptoms (dementia, diarrhea, dermatitis)
How does ATII affect the proximal convoluted tubule? PTH?
What is used as a buffer in the PCT?
- ATII: stimulates Na+/H+ exchange leading to increased Na+, H2O, and HCO3- reabsorption
- PTH: inhibits Na+/PO43- cotransport
- NH3 acts as a buffer for secreted H+
What happens in the thin descending loop of Henle?
Passively reabsorbs H2O via medullary hypertonicity - makes urine hypertonic
What is actively reabsorbed in the thick ascending loop of henle?
What is indirectly absorbed (paracellular - between cells)?
What is this portion impermeable to?
- Na+, K+, Cl- actively reabsorbed
- Paracellular reabsorption of Mg2+ and Ca2+ through (+) lumen potential generated by K+ backleak
- Impermeable to H2O
The early distal convoluted tubule actively reabsorbs ___ and ___
How does PTH affect this part of the tubule?
- The early distal convoluted tubule actively reabsorbs Na+ and Cl-
- PTH increases Ca2+/Na+ exchange (causing Ca2+ reabsorption)
In the collecting tubule, what is the MOA of aldosterone?
Insertion of Na+ channel on luminal side (through mineralocorticoid receptor)
What defect occurs in fanconi syndrome?
Reabsorptive defect in PCT - associated with increased excretion of nearly all amino acids, glucose, HCO3-, and PO43-
What is the reabsorptive defect in Bartter syndrome?
What does this result in?
Defect in thick ascending loop of Henle - affects Na+/K+/2Cl- cotransporter
Results in hypokalemia and metabolic alkalosis with hypercalciuria
What is the reabsorptive defect in Gitelman syndrome?
What does this cause?
Reabsorptive defect of NaCl in DCT - less severe than Bartter syndrome
Leads to hypokalemia, and metabolic alkalosis but without hypercalciuria
Which autosomal dominant renal tubular defect results in increased Na+ reabsorption in distal and collecting tubules?
What does it result in?
Liddle syndrome
Results in HTN, hypokalemia, metabolic alkalosis, and decreased aldosterone
In a graph showing relative concentration along proximal tubules, what is often represented by the y-axis?
TF/P = tubular fluid/plasma
What is the meaning of TF/P > 1? TF/P < 1? TF/P = 1?
TF/P > 1: solute is reabsorbed less quickly than water
TF/P = 1: solute and water are reabsorbed at same rate
TF/P < 1: Solute is reabsorbed more quickly than water
Which ion has reabsorption at a slower rate than Na+ in early proximal tubules and then matches the rate of Na+ reabsorption more distally?
Cl-
What are the 6 functions of ATII?
- Acts at ATI receptors on vascular smooth muscle causing vasoconstriction
- Constricts efferent arteriole of glomerulus
- Increases aldosterone release from adrenal gland
- Increases ADH release from pituitary
- Increases proximal tubule Na+/H+ activity
- Stimulates hypothalamus (thirst)
Through what mechanism does ANP relax vascular smooth muscle?
via cGMP, causing increased GFR, and decreased renin
What elicits renin secretion from JG cells?
- Decreased renal blood pressure
- Decreased NaCl delivery to distal tubule
- Increased sympathetic tone (ß1)
What releases erythropoietin?
Interstitial cells in the peritubular capillary bed
What are the paracrine effects of prostaglandins in the kidney?
Vasodilate the afferent arterioles to increase RBF
What can cause of shift of K+ to the outside of the cell (hyperkalemia)?
DO Insulin LAß
- Digitalis
- Hyperosmolarity
- Insulin deficiency
- Lysis of cells
- Acidosis
- ß-adrenergic antagonist
What is the calculation for the predicted respiratory compensation for a simple metabolic acidosis (Winters formula)?
PCO2 = 1.5 [HCO3-] + 8 (+/- 2)
What can lead to an increase anion gap ([Na+] - [Cl- + HCO3-]) in metabolic acidosis?
MUDPILES
- Methanol
- Uremia
- Diabetic ketoacidosis
- Propylene glycol
- Iron tablets
- Lactic acidosis
- Ethylene glycol
- Salicylates (after the initial hyperventilation)
What can cause metabolic acidosis with a normal anion gap?
HARD-ASS
- Hyperalimentation (overeating)
- Addison disease
- Renal tubular acidosis
- Diarrhea
- Acetazolamide
- Spironolactone
- Saline infusion
Type 1 renal tubular acidosis:
- Location (proximal/distal):
- Defective cell and action:
- pH:
- Causes:
- Risk for:
- Location (proximal/distal): Distal
- Defective cell and action: defect in α intercalated cell ability to secrete H+
- pH: >5.5 (hypokalemia)
- Causes: Amphotericin B toxicity, multiple myeloma, analgesic nephropathy
- Risk for: calcium phosphate kidney stones (due to increased urine pH and bone turnover)
Type 2 renal tubular acidosis:
- Location (proximal/distal):
- Defective cell and action:
- pH:
- Causes:
- Increased risk for:
- Location (proximal/distal): Proximal
- Defective cell and action: Defect in proximal tubule HCO3- reabsorption results in increased excretion of HCO3- in urine
- pH: < 5.5 (hypokalemia)
- Causes: Fanconi syndrome (Wilson disease), chemicals toxic to proximal tubule, carbonic anhydrase inhibitors
- Increased risk for: hypophosphatemic rickets
Renal tubular acidosis type 4
- Defect:
- pH:
- Result:
- Defect: Hypoaldosteronism, aldosterone resistance or K+ sparing diuretics
- pH: <5.5
- Result: Hyperkalemia
Name the disease associated with each urine cast…
- RBC casts:
- WBC casts:
- Fatty casts:
- Granular (muddy brown) casts:
- Waxy casts:
- RBC casts: Glomerulonephritis, ischemia, or malignant HTN
- WBC casts: Tubulointerstitial inflammation, acute pyelonephritis, or transplant rejection
- Fatty casts: Nephrotic syndrome
- Granular (muddy brown) casts: Acute tubular necrosis
- Waxy casts: Advanced renal disease; CRF
What are the nephritic syndromes?
ABRA
- Acute poststreptococcal glomerulonephritis
- Rapidly progressive glomerulonephritis
- Berger disease (IgA glomerulonephropathy)
- Alport syndrome
What are the nephrotic syndromes?
MD FAM
- Minimal change disease
- Diabetic glomerulonephropathy
- Focal segmental glomerulosclerosis
- Amyloidosis
- Membranous nephropathy
What can be a nephritic syndrome OR a nephrotic syndrome?
Diffuse proliferative glomerulonephritis
Mebranoproliferative glomerulonephritis
Minimal change disease
- What is the only observable change:
- Most common demographic:
- Associated disease:
- What is the only observable change:
- Effacement of foot processes on EM
- Most common demographic:
- Most common in children
- Associated disease:
- Hodgkin lymphoma (cytokine mediated damage)
Focal segmental glomerulosclerosis
- LM finding:
- EM finding:
- Common demographic:
- Associated diseases:
- LM finding: Segmental sclerosis and hyalinosis
- EM finding: Effacement of foot processes
- Common demographic: African Americans and Hispanics
- Associated diseases: HIV infection, sickle cell disease, heroin abuse, massive obesity, chronic kidney disease
Membranous nephropathy
- LM appearance:
- IF appearance:
- EM appearance:
- Demographic:
- Associated with antibody to…
LM appearance: Diffuse capillary and GBM thickening
IF appearance: granular as a result of immune complex deposition
EM appearance: spike and dome appearance; subepithelial deposits
Demographic: Caucasian adults
Associated with antibody to phospholipase A2 receptor
What is the difference between type 1 and type 2 membranoproliferative glomerulonephritis?
- Type 1: subendothelial immune complex deposits; tram track appearance tue to GBM splitting; associated with HBV, HCV
- Type 2: Intramembranous IC deposits (dense); associated with C3 nephritic factor (which stabilizes C3 convertase leading to overactivation of complement, and low levels of C3)
Diabetic glomerulonephropathy
LM appearance:
Mesangial expansion, GBM thickening, eosinophilic nodular glomerulosclerosis
Acute poststreptococcal glomerulonephritis
- Deposition of:
- Type ____ hypersensitivity
- Presentation:
- IF appearance:
- Deposition of: immune complexes (subepithelial humps)
- Type III hypersensitivity
- Presentation: peripheral and periorbital edema, dark urine (cola colored) and HTN
- IF appearance: granular appearance
In rapidly progressive glomerulonephritis (RPGN)…
- What do the crescents consist of?
- What is the prognosis?
- What disease processes can result in this pattern?
- What do the crescents consist of?
- fibrin and macrophages
- What is the prognosis?
- Poor - rapidly deteriorating
- What disease processes can result in this pattern?
- Goodpasture syndrome (type II hypersensitivity)
- Wegener (granulomatosis with polyangiitis)
- Microscopic polyangiitis and Churg Strauss
IgA nephropathy (Berger disease)…
- IgA immune complex deposition in ________
- How/when does the disease present?
- IgA immune complex deposition in mesangium
- How/when does the disease present?
- During childhood as episodic gross or microscopic hematuria with RBC casts usually following mucosal infections
- Seen with Henoch-schonlein purpura
Which glomerulonephritis is due to a defect in type IV collagen (basement membrane)?
How does it present?
Alport syndrome
Presents as isolated hematuria, sensory hearing loss, and occular disturbances
Which renal stone is radiolucent and rhomboid shaped?
Which renal stone preciptates at an increased pH and is coffin lid shaped?
Which renal stone is associated with Crohn disease and is treated with thiazides and citrate?
Which types of renal stone can form staghorn calculi?
- Which renal stone is radiolucent and rhomboid shaped? - Uric acid stone
- Which renal stone preciptates at an increased pH and is coffin lid shaped? - Ammonium magnesium phosphate
- Which renal stone is associated with Crohn disease and is treated with thiazides and citrate? - Calcium stone
- Which types of renal stone can form staghorn calculi?- Cystine and Ammonium magnesium phosphate (due to urease positive bugs)
What are the urease positive bugs that hydrolyze urea to ammonia (and can form ammonium magnesium phosphate stones)?
- Proteus mirbalia
- Staphylococcus
- Klebsiella
From which part of the tubule does renal cell carcinoma originate? What is found in the cells?
Proximal tubule cells (polygonal clear cells) filled with lipids and carbohydrates
What are the risk factors for renal cell carcinoma?
Smoking and obesity; age (men 50-70 y/o)
Which renal tumor consists of large eosinophilic cells with abundant mitochondria without perinuclear clearing and presents with painless hematuria, flank pain, and abdominal mass?
Renal oncocytoma (benign)
Wilms tumor
- Demographic:
- Gene mutation:
- WAGR complex:
- Demographic: Early childhood
- Gene mutation: Loss of function mutation of tumor suppressor genes WT1 or WT2 on chromosome 11
- WAGR complex: Wilms tumor, Aniridia (absence of iris), Genitourinary malformation, and mental Retardation
What is the most common tumor of the urinary tract system?
What can cause squamous cell carcinoma of the bladder?
- What is the most common tumor of the urinary tract system?
- Transitional cell carcinoma
- What can cause squamous cell carcinoma of the bladder?
- Schistosoma haematobium infection; chronic cystitis, smoking, and chronic nephrolithiasis
What is thyroidization of the kidney and what causes it?
Tubules can contain eosinophilic casts resembling thyroid tissue
Due to recurrent episodes of acute pyelonephritis
What are the three stages of acute tubular necrosis?
- Inciting event
- Maintenance phase - oliguric; lasts 1-3 weeks; risk of hyperkalemia, metabolic acidosis
- Recovery phase - polyuric; BUN and serum creatinine fall; risk of hypokalemia
What are two causes of acute tubular necrosis? How does each present?
Ischemic: decreased renal blood flow - results in death of tubular cells that may slough into tubular lumen (proximal tubule and thick ascending limb are highly susceptible to injury)
Nephrotoxic - Secondary to injury resulting from toxic substances (drugs), crush injury, hemoglobinuria
FENa <1% and Serum BUN/Cr > 20:
FENa > 1% (mild) and > 1% (severe) and BUN/Cr > 15:
FENa >2% and BUN/Cr <15:
- FEN<1% and Serum BUN/Cr > 20: Prerenal
- FENa < 1% (mild) and > 1% (severe) and BUN/Cr > 15: Postrenal
- FENa >2% and BUN <15: Intrinsic renal
Explain the pathogenesis of renal osteodystrophy
Failure of vitamin D hydroxylation, hypocalcemia, and hyperphosphatemia → Hyperparathyroidism and decreased serum calcium (due to hyperphosphatemia) → subperiosteal thinning of bones
What disorders are associated with ADPKD?
berry aneurysms, mitral valve prolapse, and benign hepatic cysts
Which disease causes tubulointerstitial fibrosis, shrunken kidneys, and inability to concentrate urine? What is weird about this one?
Medullary cystic disease
Medullary cysts are usually not visualized
Which cysts are common and typically asymptomatic? where are they located?
Simple cysts; usually found in outer cortex filled with ultrafiltrate
