Renal Flashcards
Acid base regulation in kidneys
- HCO3 reabsorption into blood
- HCO3 in tubule lumen binds to hydrogen H+ secreted by the brush border cell in exchange for a sodium ion from the tubule to form carbonic acid (H2CO3)
- Carbonic anhydrase type 4 splits carbonic acid into CO2 and H20 which can both then diffuse across membrane into the brush border cell
- Inside the brush border cell carbonic anhydrase type 2 combines them back to form carbonic acid which dissolves into HCO3 and H+ which are shuttled into blood using a cotransporter - H+ excretion in urine Proximal tubule uses Na-H counter transporter
- Na reabsorbed in exchange for H which is excreted into tubule lumen Distal tubule uses H+ATPase to pump H+ from blood into tubule lumen
Buffer systems used to ensure urine doesn’t become too acidic (pH>= 4.5): Ammonia and phosphate
- Ammonia combines with H+ in tubule lumen to form Ammonium (NH4+) which is excreted in urine
- H+ also combines with HPO42- to form H2PO4- which is excreted in urine
Formula for plasma clearance rate of X
(Concentration of X in urine x urine flow rate ml/min) divided by (plasma concentration of X)
Importance of inulin on clearance ratio
Inulin is a polysaccharide product by plants It is the only substance that is freely filtered (100% excreted) and NOT reabsorbed at all
Gives an accurate estimation of the GFR
Clearance ratio = Cx/Cinsulin
CR of 1 = substance X is completely filtered (same as inulin)
CR >1: substance X excreted more than it is reabsorbed
CR <1: substance X is reabsorbed more than it is excreted
Pathophys behind body’s response to dehydration
- Osmolarity increases (less fluid but same solute load) - Osmoreceptors in hypothalamus sense this -> production of ADH (vasopressin)
- Baroreceptors in atrium, aortic arch and carotid sinus sense decrease in blood volume and signal to hypothalamus to produce ADH
ADH → water reabsorption in collecting duct (aquaporin insertion) and vasocontriction → incr BP
ADH - what is it produced by - what effects does it have
- Produced by hypothalamus
- Binds to receptors in collecting ducts of kidneys and in smooth muscle of vessel walls
- In collecting duct, causes insertion of aquaporins -> H20 flows down concentration gradient from duct lumen into blood
- Causes vasoconstriction to increase BP
What happens when you drink a lot of water in terms of osmoregulation?
Decr plasma osmolarity inhibits osmoreceptors firing in anterior hypothalamus -> inhibits H20 reabsorption Baroreceptors sense increase stretch -> inhibits osmoreceptors firing in anterior hypothalamus -> inhibits H20 reabsorption
- NO aquaporin insertion into CD so H20 cannot be reabsorbed in CD so H20 is excreted
- Vasodilation to decrease BP
Cellular mechanism of ADH action on insertion of aquaporins in collecting duct
ADH binds to receptor in basolateral membrane of collecting duct (vasopressin receptor 2 which is G-protein coupled, involves conversion of ATP to cAMP via signaling cascade using enzyme adenyl cyclase)
Ultimately results in phosphorylation of aquaporin2 which is inserted into luminal membrane
Water travels down its concentration gradient from tubule lumen into bloodstream -> incr blood volume
Where is K mostly found?
Inside cells (concentration is 150) Small amount found in the plasma (4.5)
K homeostasis regulation in kidneys
REABSORPTION
- 67% K is reabsorbed in PCT (passively by ‘solvent drag’, follows the water that is reabsorbed)
- 20% K is reabsorbed in ascending LOH (Na/K/Cl co-transporter, loop diuretics inhibit)
EXCRETION
- K excretion occurs in the DCT/Collecting duct
- ‘fine tuning’ regulated by aldosterone (Na reabsorption via Na-K ATPase which exchanges Na for K)
Things that decrease ECF K concentration (and increase uptake into cells)
Ingestion of K -> plasma [K] increases
- Insulin causes glucose and K uptake into cells (via increased activity of Na/K ATPase)
- Adrenaline increases activity of Na/K ATPase to increase K uptake into cells
- Alkalosis
- Bicarb
- Ventolin/sabutamol
Things that increase ECF K concentration (excretion of K out of cells into ECF)
ATP (exercise) Cell lysis - Burns - Rhabdo - Chemo (TLS) Hyperosmolality Acidosis
Alport syndrome
X linked
Mutation in gene coding for type IV collagen (COL4a) in kidney glomerulus, eye, ear
- Kidneys: Persistent microscopic haematuria -> gross haematuria -> proteinuria -> kidney failure by age 18+
- Ears: Bilateral sensorineural hearing loss (born with normal hearing, loss occurs over time)
- Eyes: Anterior lenticonus
Ix - renal bx, genetic testing
tx - ACE inhibitor, hearing airs, replacement of occular lens, RRT/transplant
Anterior lenticonus is path pneumonic for what?
Alport syndrome
Mutation in what gene causes alport syndrome?
COL4A
Pathophys of Anaemia of CKD
Tx
Primarily the result of inadequate EPO production by failing kidneys
Other contributory factors = Fe deficiency, folic acid or B12 deficiency, decreased erythrocyte survival
Recombinant EPO used as treatment if other above causes are treated
Findings of renal tubular acidosis (biochemical and clinical)
Biochemical: Normal anion gap metabolic acidosis Hyperchloraemic
Normal renal function despite this
K low in types I,2 and high in type 4
Clinical: Poor growth, Polyuria, Dehydration, Ricketts (from chronic metabolic acidosis leading to reabsorption of minerals (Ph) from bone to buffer this)
What is the primary defect that causes type II RTA?
Impaired bicarb reabsorption in prox tubule leads to aciodosis in blood
Urine pH>7
Serum bicarb usually >10
Hypokalaemia
What is the primary defect that causes type I RTA?
Impaired hydrogen ion secretion (H+ ATPase isn’t working) into tubule > leads to acidosis in blood
Present with Ca renal stones (due to high tubular Ca)
Urine pH >5.5
Serum bicarb <10
Hypokalaemia
What is the primary defect that causes type IV RTA?
Decr aldosterone secretion or resistance to aldosterone
> impaired hydrogen ion secretion into tubule (Aldosterone stimulates secretion of H+ via the H+/ATPase in the collecting tubules)
> leads to acidosis in blood
Hyperkalaemia (Aldosterone stimmulates Na/K ATPase)
Urine pH < 5.5
Serum bicarb usually >10
Nephrotic syndrome Key ft Causes and treatment
Key fts: proteinuria (>3.5g protein lost/day), hypoalbuminaemia, oedema, hypercholesterolaemia
Causes
- Primary/idiopathic due to minimal change disease (85%) or focal sclerosis glomerulonephritis (10-15%) or membraneous nephropathy
- Secondary - alport syndrome, SLE, HSP, GN Pathophys - Leaky glomerulus -> proteinuria and low serum albumin
Ix - Urine - protein, lipids, fatty casts Bloods - incr lipids
Cx - Hypercoagulable state (antihrombin III lost in urine) - Incr infx risk (Ig lost in urine)
Tx Daily urine dips Daily weight No added salt in diet Albumin + furosemide Oral pred
Cyclophosphamide - second line if relapsing or steroid dependent nephrotic syndrome Penicillin if suspected peritonitis
Mx of nephrotic syndrome with ATYPICAL features (and what are atypical features)
ATYPICAL: HTN, haematuria, age <12mo or >12yrs
Further ix (atypical nephrotic syndrome)
Complement - low C3/4 in SLE and MPGN
ANA - SLE ‘
Hep B if at risk
Biopsy if steroids resistant after 4-6 wk therapy or atypical features
Causes of normal anion gap metabolic acidosis
Pneumonic = CAGE
C = chloride excess (eg. NaCl)
A = acetazolamide (Carbonic anhydrase inhibitor, incr bicarb excretion), Addison’s
G = GIT causes – diarrhoea, vomiting, fistula (pancreatic, ureters, biliary, small bowel, ileostomy)
E = extra – RTA
Causes of widened anion gap metabolic acidosis
K = ketoacidosis
U = uraemia (renal failure)
L = lactic acidosis (ischaemia)
T = toxins [ethylene glycol, methanol, aspirin (salicyclates), metformin]
What is the most common genetic mutation in autosomal recessive polycystic kidney disease
Mutation in PKHD1 gene (polycystic kidney and hepatic disease)



