Renal Flashcards
What’s unique about the kidneys arterial supply?
Capillary beds in kidneys drain into capillary beds, whereas capillary beds in the rest of the body drain into veins. This is why its called the renal portal system
What is the general job of the glomerulus?
Glomerulus filters almost everything out of the blood into the ultra filtrate (urine(
What is the general job of the proximal convoluted tubule?
Reabsorp almost everything from the utrafiltrate back into the blood
What is the general job of the loop of henle?
Dilute the urine and create a medullary concentration gradient
What is the general job of the distal convoluted tubule. and collecting ducts?
Concentrate the urine and control acid base. If ADH and a medullary concentration gradient
What are the 3 components/layers of the Renal Corpuscle?
- Capillary endothelium - faces lumen,
- GBM
- Podocyte - faces urinary side
All negatively charged
Passage of material through filter depends on size and charge (small, positive molecules get through)
What is the route of blood to urine?
Arterial blood –> afferent arterioles –> glomerulus –> capillary endothelium –> GBM –> podocytes –> urinary space (Bowmans capsule) –> proximal tubule
Where is the macula densa located? What do they do when they sense low Na? High Na?
Distal convoluted tubule
Low Na: stimulates juxtaglomerular cells to release renin –> ultimately vasodilates afferent arteriole to increase GFR
High Na: no renin released. Vasoconstriction of afferent arteriole to reduce GFR
What is the job of the macula densa?
It senses Na+ and Cl- exiting the distal thick ascending LOH
Depending on this will respond
What type of cells produce and release renin? In response to what?
JG cells produce and release renin in response to low renal perfusion. Signal comes from the macula densa when the Na is low
How much is absorbed of each in the PCT?
glucose, AA, Na, K, urea, phosphate, Ca, bicarb, H2O
Glu: >99%
AA: >99%
Na and K: 2/3 in PCT, also reabsorbed in LoH + DCT
Urea: ~50%
Phosh: 80-90%
Ca: >90% ionized or chelated Ca absorbed
Water: >99%
Describe the resorption of bicarbonate in the PCT
Na gets counter transported with hydrogen ions (Na out, H+ in) - basolateral side. Uses 3Na-2K-ATPase pump (active)
As H+ comes into the cell it combines with H2CO3 inside the tubular lumen.
The enzyme carbonic anhydrase converts to H2O + CO2 (easily transported through membrane).
The CO2 is transported to the PCT and combines with H2O through carbonic anhydrase to form H2CO3 (BICARB!)
Describe the absorption of glucose in the PCT?
Luminal side: cotransported with Na
Basolateral side: facilitated diffusion according to concentration gradient
The renal threshold for phosphate is (low/high). What hormone increases renal phosphate excretion in the PCT?
LOW
PTH increases renal phosphate excretion
What type of transport is happening in the thin ascending LOH? Thick ascending?
Thin – passive transport
Thick – active transport
How is Na absorbed in the luminal side of PCT?
Cotransported with glucose, AA, phosphate
How is Na absorbed in the basolateral side of PCT?
NaK ATPase and Na-bicarb cotransporter
What is the MOA of furosemide?
Inhibits the action of Na-K-2Cl cotransporter in the thick ascending LOH. It works by not making the urinary concentration gradient.
What are the 2 main types of cells in the DCT? What distinguishes them?
- Principal cells
- Resorption of Na, secretion of K based on ALOSTERONE (increases # of open luminal Na+ channels and basolateral Na+ pumps); resorption of H2O based on ADH (increases # of aquaporins)
-Also play a role with ADH (remember that with ADH there is no active transport of H2O, just increase in the # of aquaporins) - Intercalated cells - acid-base regulation
What’s the difference between alpha and beta intercalated cells in the DCT?
Alpha: secrete acid in the form of H_ ions on luminal side –> active transport
- This is broken in distal (type 1) RTA
Beta: secrete base in the form of bicarbonate ions on the basolateral side –> passive transport
MOA and SE of spironolactone
MOA: K-sparing diuretic or mineralcorticoid-receptor antagonist
-Competitively inhibits aldosterone in the DCT –> increase excretion of Na, Cl, water + decreased excretion of K, ammonium, phosphate
SE: GI, electrolyte (hyperkalemia, hyponatremia)
What is the major tubular site for aldosterone?
Principal cells in the distal portion of DCT and collecting ducts
What is the mechanism for aldosterone? What are the stimuli for aldosterone release?
Stimulation of NaK ATPase pump - basolateral
Stimuli for aldosterone:
1. Increased extracellular K
2. Increase Ag II levels (when hypotension)
Describe the pathogenesis for diabetes insipidus in the nephron
DI have a lack of ADH. Without ADH the permeability to water decreases in the distal tubules and collecting ducts. This leads to the kidneys excreting large, dilute volumes.
Name 4 sequelae of angiotensin II activation
- Blood vessel constriction (increase BP)
- Aldosterone release (increase Na and H2O resorption, increase ECF)
- ADH release (increase water resorption, increase ECF)
- Sympathetic NS stimulation (increase BP)
What is the pathogenesis of Type I renal tubular acidosis?
Alpha intercalated cells in the distal portion of the DCT and collecting ducts are not working. These cells usually secrete acid in the form of H.
What characterizes RTA? What are the types?
Hyperchloremic metabolic acidosis
Types:
-Proximal (type II) RTA
-Distal (type I) RTA
- Distal (type IV) RTA
What would the urine pH be for the Types:
-Proximal (type II) RTA
-Distal (type I) RTA
Types:
-Proximal (type II) RTA: acid pH (<6), no nephroliths or nephrocalcinosis, mild metabolic acidosis, can excrete other solutes such as AA, glu, phos, Na, K
-Distal (type I) RTA: alkaline pH ((>6), more severe metabolic acidosis, can have nephroliths and nephroclcinosis, no concurrent defects of PCT resorption
What is the pathogenesis for proximal (type II) RTA?
Defect in the basolateral membrane Na+ HCO3- cotransporter. HCO3- leaks into tubular lumen, preventing bicarb reabsorption and leading to metabolic acidosis. Can occur alone or with Fanconi syndrome or other proximal tubular defect.
What are the complications of proteinuria?
Azotemia
Hypoalbuminemia –> edema
Hypertension
Thromboembolism
What MHC is expressed in proteinic dogs as part of the inflammatory response?
MHC II - seen because of lymphocyte recruitment
What percentage of dogs with PLN are hypercoagulable?
~89%
What is the prevalence of thromboembolism in PLN dogs?
25%
What is the mechanism for hypercoagulaibility in PLN?
Antithrombin loss
Platelet activation
Hyperfibrinogenemiaa
Increased factors V, VIII
Thrombocytosis
Decreased RBC deformability
Increased vWF
Fibrinogen and alpha-2 macroglobulin accumulation
Inhibition of fibrinolysis
What is the incidence of hypercholesterolemia in glomerular disease?
79-86%
What is nephrotic syndrome?
Proteinuria
Hypoalbuminemia
Ascites
Hypercholesterolemia
What is nephritic syndrome?
2ry to renal inflammation and acute glomerular swelling
Common in humans, uncommon in dogs
Can see 2ry to Lyme disease - nephritis-like syndrome
Hematuria/RBC casts –> proteinuria
Edema
Hypertension
Azotemia
OLIGURIA
What is the major determinant of glomerular filtration? What is the limit of the GBM?
SIZE
but also negative charge
GBM limits 60-70,000 daltons
Albumin is 69,000 daltons AND has a negative charge
What are microscopic changes to the glomerulus that we see with glomerular disease?
-Podocyte effacement
-Enlargement of the diaphragm
-Loss of negative charge
Post-renal causes of proteinuria
Urinary system - no associated w/kidney
UTI
FLUTD/Cystitis
Urolithiasis
Prostatitis
Neoplasia (TCC, prostatic carcinoma, etc)
Intact male dog (semen can contribute, but eliminating seminal fluid is the only way to know – neuter)
Where does the proteinuria come from in pre-renal?
Overwhelm reabsorptive capacity of the PCT
-Hemoglobin
-Myoglobin
-Bence-jones proteinuria
Where does the protein come from in renal proteinuria?
Funtional/physiologic: transient changes in selectivity of glomerulus (seizures, fever, exercise, stress)
Pathologic:
-Glomerular: decreased per selectivity – most common cause of persistent high magnitude proteinuria (>5UPC)
-Tubular: decreased protein reabsorption (1-3UPC)
-Interstitial: exudation of proteins to the urinary space
Does hematuria affect the UPC?
Microscopic hematuria only minimally affects UPC. Blood does NOT affect UPC unless it changes the color of the urine
Does pyuria affect the UPC?
81% of dogs w/pyuria have normal. UPC
Does semen affect the UPC?
May cause false-positive results for protein and blood on dipstick
What is the level of protein detection in the dipstick, SSA, microalbuminuria?
Dipstick: 30mg/dL
SSA: 5mg/dL
Microalbuminuria: 1mg/dL
Does pooling the urine for UPC change the magnitude compares to single catch?
No
Is there a difference between drip or dip in the urine dip stick results?
Dip > drip
Increases variability with drip method - pH, blood, glucose.
Which stain do we use for diagnosis of amyloidosis in renal biopsies using light microscopy?
Congo red
What can you see with the H and E stain using light microscopy?
Cellularity, wall thickness, inflammatory cells
What can you see with the PAS stain using light microscopy?
Basement membrane and matrix
Which stain do we use for diagnosis of immune complexes in renal biopsies when using light microscopy?
Masons trichrome
What does fluorescent stains in renal biopsies diagnose?
Immune complexes.
What part of the kidney do we obtain for a renal biopsy?
Cortex ONLY, no medulla
Run light microscopy, electron microscopy, immunofluorescence
Need 20-25 glomerular tufts for 90% confidence
What. are contraindications for renal biopsies?
IRIS Stage 4 or greater (crea >5)
Polycystic kidney dz
Renal abscess, infx
Hydronephrosis
Coagulopathy
Uncontrolled hypertension
What are the 3 most common types of glomerular diseases?
Membranoproliferative glomerulonephritis (MPGN)
Membranous nephropathy (MN)
Amyloidosis
Account to 66% of all glomerular diseases
What is the most common glomerular disease in dogs?
Membranoproliferative glomerulonephritis – 20-60%
No sex predilection
Mean age: 7-10Y
Slowly progressive, EXCEPT BERNESE MOUNTAIN DOGS
What % of dogs with MPGN are hypoalbuminemic?
75%
What % of dogs with MPGN are hypertensive?
40%
What % of dogs with MPGN have a UPC >1.6?
80%
What are the findings you can find in the electron microscopy in a dog with membranoproliferazive glomerulonephritis?
-Thickened capillary loops
-Mesangial hypercellularity
-Identification of immune complexes on the sub endothelial side of the glomerular basement membrane
What are the 2 types of MPGN? How do you tx it?
Type I (mesangiocapillary GN): often caused by infectious disease (mainly tick borne)
Type II (Dense Deposit Disease): rare in dogs. Not associated w/infectious dz.
TX: tx infectious dz or neoplasia
What is the most common cancer that causes proteinuria?
Lymphoma
What is the most common glomerular disease in cats? And the second most common in dogs?
Membranous nephropathy - NOT an inflammatory disease
M>F
The rate of nephrotic syndrome with membranous nephropathy is (high/low).
HIGH - 80% have mild to severe hypoalbuminemia
What are the 2 forms of membranous nephropathy? What is the tx?
Primary/Idiopathic - immune complexes on subepithelial aspect of glomerular basement membrane
-Reaction with unbound antibody and fixed antigen (podocyte) on urinary side
Secondary - circulating immune complexes also present in the mesangium and/or subendothelial space
-Circulating immune complexes and complement driven mechanism independent of inflammatory cells
Tx: IMMUNOSUPPRESSION
What are the common finings in electron microscopy in patients with amyloidosis?
Extracellular deposition of proteins with beta-pleated sheet
What’ the difference between reactive and familial amyloidosis>
Reactive amyloidosis – amyloid deposits in glomerulus
Familial amyloidosis – amyloid deposits in renal medulla
Who is predisposed to reactive amyloidosis? What’s the mean UPC?
F>M
Mean age: 7-9YO
Mean UPC: 12.7
What % of dogs w/reactive amyloidosis are azotemic?
50% have creatinine >1.6
What cat breeds are predisposed to familial amyloidosis? What dog breed is predisposed?
Abyssinian/Siamese
Shar Pei
What are the microscopic changes in the kidney of a cat with familial amyloidosis?
Medullary fibrosis and papillary necrosis
Where else do siamese deposit amyloid other than the kidney?
Liver
What is the tx of familial amyloidosis?
Colchine - impairs release of SAA from hepatocytes
DMSO - decreases SSA/decreases inflammmation
Is proteinuria common in Shar Pei fever?
Not as common given that the deposits are in the medulla
What systemic diseases are related to glomerular sclerosis (scarring of the gomerulus)?
DM, hypertensive nephropathy - end stage
What dog breed is predisposed to hereditary nephropathy? Where is the defect in the GMB?
X-linked in Samoyeds
Defect in GBM collagen type IV
What mutation to cocker spaniels have in their collagen chain of the kidneys?
COL4A4 - GBM disease
What is the pathogenesis of minimal change disease nephropathy?
Dysfunction of T-cells –> increase lymphokines –> loss of (-) charge of GBM –> increased permeability
Why are omega-3 FA recommended in proteinuric patients?
Reduce inflammation and vasoconstriction
Lower mortality, increased renal function, reduced proteinuria and cholesterol
What’s the MOA of thienopyridines (Clopidogrel and Ticlopidine)?
-irreversibly inhibits binding of ADP to platelet P2Y12 receptor
-this impairs platelet release reaction and ADP mediated activation of GPIIb/IIIa, reducing the primary and secondary aggregation response
-metabolized by cytochrome p450
-platelet inhibition occurs 3 days after starting tx
-ticlopidine – but associated with unacceptable GI side effects
What is the MOA of aspirin?
Irreversibly inhibits COX-1 (catalyze conversion of arachidonic acid to PGH2- precursor for PGD2 - PGE2, PGI2, and TXA2 (thromboxane A2))
SE:
-GI upset
-acidosis (with OD)
-probably less common with lower anti-platelet doses)
What is the MOA of heparin?
Binds to AT –> inactivates procoagulant activity of factor IIa (thrombin). Also inhibits activatino of factor XIII and increases release of lipoprotein lipase –> clears circulating lipids
What is the MOA of unfractioned heparin?
-heterogenous mixture of molecules of differing molecular weights (3000-30,000 daltons)
-~1/3 of molecules that possess a pentasaccharide sequence that binds to AT and accelerates its interaction with thrombin (IIa), and Xa . (also IXa, XIa, XIIa but these aren’t as important
-thrombin inactivation requires formation of a ternary complex involving heparin, AT, and thrombin (only heparin molecules with more than 18 monosaccharide units can inactivate thrombin)
-indirect anticoagulant – exerts most of its activity through potentiation of AT
-anti-Xa:anti-IIa ratio: 1.0
-unpredictable anticoagulant effect in dogs and cats
What is the MOA of enalapril and benazepril?
-block ACE –> decrease formation of angiotensin II from angiotensin I (competes with AT I with higher affinity)
-preferentially dilate efferent arteriole (and thus may decrease GFR)
-may temporarily reduce aldosterone levels
-increase circulating bradykinin (inhibits bradykinin degeneration)
-balanced vasodilators (though weak)
-mostly renal excretion except benazepril (biliary excretion 50% in dogs, 85% in cats)
-enalapril 80% excreted through kidney
SE:
-hypotension
-decreased GFR
-hyperkalemia (due to decreased GFR and decreased aldosterone)
-GI – vomiting, diarrhea, anorexia
What is the MOA of telmisartan?
ARB - block angiotensin II subtype I receptors
-binding of subtype 2 is preserved
-Avoids ACE proteolytic pathways which can increase AgII production
-Telmisartan is more effective due to higher affinity and slower dissociation from the Ag-1 receptor
First line therapy for proteinuria
What’s the tx for immune mediated glomerual diseases?
Mycophenolate - recommended first choice
Cyclophosphamide
Glucocorticoids - recommended short term
MOA and SE cyclophosphamide
Alkylating agent
Nitrogen mustards: N-7 position on guanine base most common site of alkylation; leads to mispairing with thymidine or strand breakage
SE: myelosuppression, GI, renal tox (sterile hemorrhagic cystitis, hematuria), cardiac, hepatic, pulmonary tox
MOA mycophenolate
-pro-drug hydrolyzed in liver to form mycophenolic acid
-cytostatic for lymphos
-inhibits inosine monophosphate dehydrogenase (necessary for purine biosynthesis)
-selective inhibitor of T and B cell proliferation
When would you expect to see improvement with immunosuppressive therapy?
At least 8 weeks before altering or abandoning immunosuppressive trial
If no response in 3-4 mo - d/c immunosuppression
What will cause a false positive for protein in the urine dipstick test?
High pH or concentrated urineW
What will cause a false negative for protein in the urine dipstick test?
Low pH, dilute urine, Bence-jones protein
Describe the IRIS CKD Staging
Name the DDX for an acute kidney injury
-Toxin: NSAIDs, grapes (dogs), Lillies (cats), EG, aminoglycosides, cisplatin, omnipaque, heavy metals, hemoglobinuria/myoglobinuria, envenenomation, melamine/cyanuaric acid, expired tetracyclines
-Infectious: Lepto, Borrelia, Leishmania, peel (bacterial, fungal)
-Ischemia: hypovolemia, decreased CO
-Inflammation: pancreatitis, trauma, sx
-Hypercalcemia
-Hyperviscosity
-UO
Name the ddx for feline LUTD
-Bacterial cystitis
-Uroolithiasis
-Urethral stricture
-Urethral trauma
-Neoplasia
-Urethral plug
-FIC
Risk factors for FLUTD in cats
Persian, Manx, Himalayan
Middle aged (4-7y)
Male
Overweight
Neutered
Which crystal is implicated in the pathogenesis of FIC?
Struvites. Over 80% of mineral urethral plug
What pro inflammatory cytokines/chemokines are present in higher concentration in cats with FIC?
CXCL12
IL12
IL18
FIt3L
MOA and SE of prazosin
MOA: alpha1 adrenergic blocker –> relaxes vascular smooth muscle
SE: high BW, GI, Neuro signs, nictitans elevation
MOA and SE of bethanecol
MOA: cholinergic - increases tone of detrusor muscle in the bladder
SE: GI, CV (hypotension, tachycardia), elevated tbil, AST
What diet do you use in FIC cases
Acidifying, low in Mg
Also have tryptophan (serotonin precursor) + alpha-casozepine (partial GABA agonist- anxiolytic)
Considering the physiology of renal blood flow through the nephron, if a therapy decreased the blood pressure in the afferent arteriole a ______ in GFR might occur.
Decrease
The proximal tubule reabsorbs what % of Na and water?
65%
Tx for CDI
SE and MOA of drug
Desmopressin:
MOA: synthetic vasopressin (ADH) that acts on V2 receptors – increases urine osmolalality + decreasing net urine production
SE: ocular irritation, neuro signs with hypernatremia, hypersensitivity
NOTE: also causes dose-dependent increase in vWF by relesing vWF from endothelial cells and macrophages
T/F: Vitamin D enhances the expression of apical calcium transport channels and intracellular calcium binding proteins within the cells of the distal convoluted tubule and collecting duct.
True
What cell is primarily responsible for the selectivity of the glomerular filtration barrier?
Podocytes
What is the limit in daltons for the GBM?
Limits 60-70,000 daltons
Albumin: 69,000 daltons, negatively charged
Which hormones are secreted by the posterior pituitary?
Oxytocin and ADH
What are the common dog breeds for renal dysplasia?
-Lhasa Apso
-Poodles
-Shih tzus
-Soft coated wheaten terrier
-Chow Chow
-Alaskan Malamute
-Mini schnauzer
-Dutch kooiker (decoy dog)
What are the 3 dog breeds predisposed to polycystic kidney disease?
-Bull terrier (dominant gene)
-Cairn terrier (recessive gene)
-Westie (recessive gene)
What breed is predisposed to X-linked hereditary glomerular basement membrane defect?
Samoyeds
What breed is predisposed to primary MPGN?
Doberman
What dog breeds are predisposed to amyloidosis familial glomerulopathy?
Shar pei, English Foxhound, Beagle
What dog breeds are predisposed to immune-mediated familial glomerulopathies?
Soft coated wheaten terrier
Bernese mountain dog
Brittany spaniel (type I MPGN secondary to C3 deficiency)
What immune-mediated familial glomerulopathy do Bermese mountain dogs have?
Type I MPGN –> positive for C3 and IgM
What breed is predisposed to Fanconi Syndrome?
Basenji
Which breed is predisposed to reflux nephropathy with segmental hypoplasia?
Boxer
Which breed is predisposed to multifocal cystadenocarcinoma familial glomerulopathy?
GSD
Which breed is predisposed to telangiectasia familiar glomerulopathy?
Corgi
Which cat breed is predisposed to polycystic kidney disease?
Persian (autosomal dominant)
Which cat breeds are predisposed to familial amyloidosis?
Abyssinian, Siamese, Oriental
What is the most common cause of primary polyuria in SA?
Secondary nephrogenic DI
What are the ddx for PU/PD based on the mechanisms of action?
CDI
Primary NDI
Secondary NDI
-Cushings
-Addisons
-Hyperthyroidism
-Hyperaldosteronism
-Liver dz
-Pyelo
-Pyo/E coli endotoxemia
-Lepto
-Acromegaly
-Leiomyosarcoma
-Drugs (steroids, phenobarbital)
Osmotic diuresis
-DM
-CKD
-1ry renal glycosuria
-Fanconi
-Post-obstructive diuresis
-Drugs (osmotic diuretics)
-High salt diet
Low renal medullary tonicity
-Renal medullary washout
-Low protein diet
Other/unknown
-Polyuric phase of AKI
-Syndrome of inappropriate ADH secretion
-Splenic hemangiosarcoma
-Pheo
What is important to have in mind in a patient with glycosuria?
Glycosuria can increase the USG by 0.04 for each g/dL of glucose in the urine. Urine can be marked as concentrated when it’s not
What pH do struvites grow in?
Alkaline due to UTI
How long do you tx struvite stones?
2-4 weeks post resolution of radiographic/US stones and negative urine culture
What is different in dogs and cats w struvite stones?
Dogs - associated w/UTI
Cats - usually sterile/not associated with UTI
What medication can you consider as adjunctive for struvite stones (other than antibiotics)?
Urinary acidifier such as D, L-methionine
What are predisposing factors to CaOx stones other than breed?
Hypercalcemia
Hypercalciuria
Increased oxalate excretion
Acidic urine
Decreased urine vol/highly concentrated urine
High protein diet?
What is the USG target for dogs with CaOx stones?
Dogs: <1.020
Cats: <1.030
What medication can be considered for dogs with recurrent CaOx stones and why?
Thiazide diuretics (hydrochlorothiazide) - reabsorb filtered calcium
- If not hypercalcemic
Potassium citrate to alkalinize urine
What is the target pH for minimizing recurrence of CaOx stones?
pH > 6.5
No crystalluria
What type of pH do Calcium Phosphate Hydroxyapatite stones form in?
Alkaline (bc concomitant urease-producing UTI)
What happens if you use allopurinol alone in a Dalmatian with urate stones?
Xanthine stones if not doing concurrent protein restricted diet
What gene mutation causes urate stones in Dalmatians?
SLC2A9 Gene Mutation - inherited alteration of urate transported
What gene mutation is associated with cystine uroliths in cats?
Missense mutation in SLC3AI gene
Describe the purine metabolic pathway
Purine –> hypoxanthine –> xanthine –> uric acid –> allantoin
What cat breeds are predisposed to forming CaOx stones?
Persian and Himalaysn
What is the cause of cystine stones in dogs?
Genetic defect - reduced ability of the kidney’s proximal tubule to resorb cystine and other AA –> increased cystine in urine –> cystine stones
What is thiola used for?
Thiola - tiopronin or 2-MPG - increase solubility of cystine
Can cause aggression, myopathy
What dog breeds are predisposed to xanthine stones?
Toy Manchester terrier, KCCS, English springer spaniel - proximal tubular defect
What’s the MOA of allopurinol?
Inhibits xanthine oxidase (enzyme that converts xanthine to uric acid)
Which uroliths CANNOT be dissolved?
Xanthine, CaOx, Ca Phosphate (unless >70% struvite), Silica
Which uroliths CAN be dissolved?
Struvite, urate (if no underlying liver dz), cystine
What breeds are predisposed to silica cystoliths?
Yorkies <3, shih tau, Lhasa, Goldens, GSD
What are predisposing factors for silica cystoliths?
- Consuming diet or meds w/large amount of silica in soil or certain plants (corn gluten, whole grains, wheat hulls)
-Active or inactive ingredient of meds containing silica
-Some antacids: magnesium trisilicate
What are causes of hypernatremia? List mechanism
Loss of water in ECF: CDI (lack of ADH), NDI (renal disease that does not respond to ADH)
Excess Na in ECF: over hydration, hypothalamic lesions
How much can you correct hyponatremia per day?
<10-12 mmol/L
What are causes of increase capillary pressure leading to edema?
-Excess renal retention of Na and water: acute or CKD, mineralocorticoid excess–> leads to SHT
-Increase venous pressure and venous constriction: CHF, venous obstruction, failure of pumps (paralysis, immobilization, failure of venous valves)
-Decrease arteriolar resistance: vasodilatory drugs, insufficiency of SNS, excess body heat
What are causes of low plasma proteins leading to edema?
Nephrotic syndome
Denuded skin areas
Failure to produce proteins: liver disease, protein/caloric malnutrition
Describe causes (cellular level) of increased GFR
-Increase glomerular capillary filtration coefficient
-Increase rate of blood flow to glomerulus
-Increase glomerular capillary hydrostatic pressure
Describe causes (cellular level) that decrease GFR
-Increase Bowmans capsule hydrostatic pressure
-Increase glomerular capillary colloid osmotic pressure
-Increase resistance of afferent arteriole
What’s the effect of efferent constriction on GFR?
Biphasic effect
-If constriction of efferent arteriole is severe –> colloid osmotic pressure exceeds the increase in glom capillary hydrostatic pressure caused by efferent arteriole –> decrease GFR
-If moderate level of constriction–> slightly increase GFR
What’s the effect of afferent constriction on GFR?
Decrease GFR
What’s the effect of strong activation of sympathetic NS on GFR?
Constriction of renal arterioles –> decrease renal blood flow –> decrease GFR
What’s the effect of NE and Epi on the kidney
Constriction of afferent and efferent arteriole = decrease GFR
What’s the effect of angiotensin II on afferent and efferent arterioles of the kidney
Constricts the EFFERENT
Increases glomerular hydrostatic pressure while decreasing renal blood flow –> helps prevent decreases in glomerular hydrostatic pressure and GFR
What does urinary excretion =
Excretion = Filtration - Reabsorption + Secretion
How much of the CO is filtered through the kidney?
20%
Electrolytes with nephrogenic DI – which electrolyte could be decreased?
Cl low
Na, Ca HIGH
Nephrogenic DI – kidneys unable to respond to ADH
ADH 🡪 reabsorb water in distal and cortical tubules
Plasma osmolarity should be high normal to increased
MOA of mannitol (osmotic diuretic)
Increase ECF and plasma volume –> increase renal blood flow –> traps water in tubule –> diuresis
WHats the gold standard for diagnosing anti-GBM diseases?
Direct immunofluorescence for immunoglobulin – typically show a strong linear ribbon-like appearance
What is ANCA?
Anti-neutrophilic cytoplasm antiBODY disease
-Autoantibodies specific for neutrophils and monocyte granule proteins
-Neutrophil degranulation causes small vessel vasculitis
With glomerulonephritis associated with SLE, where would we see the defect?
sub endothelial and/or subepithelial
Main extracellular electrolyte
Na
Main intracellular electrolkyte
K
What factors regulate the NaK ATPase?
Insulin (moves K into cell)
Catecholamines
Thyroid hormone
K balance in body
Chronic disease (heart, renal)
How do catecholamines affect K?
Alpha: impair K entry to cell
Beta: promote K entry to cell
How does K shift in acidemia? Alkalosis?
Adisosis: movement from ICF–>ECF
Alkalosis: movement from ECF–>ICF
Where do the thiazide diuretics work? How?
Distal convoluted tubule
Inhibit Na/Cl cotransporter in the distal convoluted tubule; actions: 1) block electrolyte resorption and loss of H20, 2) increased K and H secretion in the distal tube,
-initially have a hypercalciuric effect, but with continued therapy calcium excretion is significantly decreased (in normal dogs, hydrochlorothiazide by not chlorothiazide had this effect); causes subclinical volume depletion resulting in proximal tubule reabsorption of Na and Ca; this effect is blunted when using high Na diet
-paradoxically decrease urine production in dogs with diabetes insipidus
Which cells are responsible for K excretion in the kidneys?
Principal cells in the collecting tubule
Which cells in the cortical collecting ducts secrete bicarb?
Intercalated type B cells
polarity reserved com0ared to type A cells
WHats the most important hormone for urinary K excretion?
Aldosterone
What promotes aldosterone release?
AgII
Hyperkalemia
ACTH
Hyponatremia
Acidemia
What inhibits aldosterone release
Dopamine and atrial natriuretic peptide (ANP)
What step is carbonic anhydrase required for?
dissolved CO2 -> carbonic acid (H2CO3)
What is the strongest stimulus for aldosterone?
Hyperkalemia
What stimulates ADH?
Osmoreceptors in the supraoptic nuclei due to high osmolarity, dec. blood volume, dec. blood pressure
What does the juxtaglomerular apparatus secrete?
Renin
Which factor decreases GFR?
Kf
Glomerular onc pressure
Glom hydrostatic pressure
Hydrostatic pressure of bowman’s capsule
Decreased onc pressure of Bowman’s capsule
Low Kf, high glomerular onc pressure, low glom hydrostatic pressure, increased hydrostatic pressure of bowman’s capsule, decreased onc pressure of Bowman’s capsule
Effect of hormones on GFR:
-Epi/NE and endothelin
-NO
-Prostaglandin
-Bradykinin
-Increased Epinephrine/NE and endothelin secretion = decrease GFR
-Decreased Ang II (constricts efferent arterial, normally as a BP protective measure) = decreased GFR
-Decreased NO (dilates afferent art.) = decreased GFR
-Decreased prostaglandins and bradykinin (increase renal blood flow) =decreased GFR
Parasympathetic innervation to the urethra
- Pelvic nv
Renal hemorrhage
normal serum, + occult blood, red supernatant
What does oxaloacetate depletion lead to in terms of diabetes
= ketone formation
- Pressure natriuresis with increased aldosterone to prevent increased sodium
Fractional excretion (urinary) of Na <1%
🡪 relative volume decrease (SIADH, low aldosterone, Lasix admin)
Fractional excretion of K - what’s normal, what’s the use
Less than 4% in non-renal causes
Can help distinguish between renal and non renal causes of HYPOkalemia
What is affected with amino glycoside toxicicty
aminoglycoside toxicity - proximal convoluted tubule
Syndrome of inappropriate ADH- effect on GFR
Normal GFR
Diagnosis: High sodium, low serum osmolality
: central diabetes insipidus
What GN is least likely to be responsive to immune suppressive therapy?
Amyloidisis
DDAVP in psychogenic PD dog - what would you expect to see in BW?
—low sodium
Calcitriol in CKD
Vitamin D analog – with PTH and calcitonin will regulate Ca homeostasis
What would concentrated urine or a high pH do to the dipstick protein measurement
False positive
What would dilute urine, low pH, or hence jones proteins do to the dipstick
Fasle negative
Phenylpropanolamine MOA
Alpha agonist - inducing norephinephrine release (indirect sympathomimetic, affects alpha more than beta receptors)
What nephropathy do dogs with GI or liver disease get?
IgA nephropathy –> mesengial proliferative GN
Factors that influence renal K excretion
Na intake
K intake
Mineralcorticoids
Hydrogen ions
Diuretics
What’s the high K+ phenotype? Inheritance? Breed
Active NaK ATPase maintains intracellular K
Autosomal recessive trans
Shibas, akita, kinda
May also accumulate glutathione – increases susceptibility to oxidative injury
How can low K affect the kidneys
Hypokalemic nephropathy
Renal vasoconstriction of afferent arteriole –> decreased renal blood flow and GFR
impaired responsiveness to ADH –> PU/PD
What will albuterol toxicity do to the K?
Hypokalemia
What breed of cats is predisposed to HYPOkalemia periodic paralysis
Burmese
recurrent episodes of limb weakness, cervical ventroflexion
increased CK
What changes to bloodwork would vomiting lead to?
Hypochloremic metabolic ALKALOSIS – tx with 0.9% NaCl and KCL
What causes hyperaldosteronism in a cat?
50/50 - adenomas or adenocarionmas
What’s the anion gap formula? Whars normal
AG = (Na+ + K+) - (CL- + HCO3-)
Norma;: 18-24
Strong ion gap increases with unmeasured strong anions
Strong anion gap formula
Dog = (alb) x 4.9 - AG
Cat = (alb) x 7.4 - AG
Normal: -5 to +5 mEq/L
DDX for High AG metabolic acidosis
Ketoacidosis
Lactic acidosis
Uremic acidosis
Intoxication (EG, salicylates, metaldehyde)
Ddx for normal AG metabolic acidosis
Addisons
Diarrhea
Renal tubular acidosis
Post-hypocapnia
Iatrogenic (CAIs, ammonium, chloride, TPN)
Describe the classic metabolic acidosis pattern
Low pH
Low bicarb
Low CO2 (compensation)
Describe the classic respiratory acidosis pattern
Low pH
High bicarb (compensation)
High CO2
Describe the classic metabolic alkalosis pattern
High pH
High CO2 (compensation)
High bicarb
Describe the classic respiratory alkalosis pattern
High pH
Low CO2
Low bicarb (compensation)
DDX for respiratory acidosis
Large airway obstruction
Small airway disease
Pulmonary parenchymal disease
Restrictive pleural space disease
Neuromuscular dz causing resp muscle failure
Increased CO2 production w hypoventilation
Iatrogenic (mechanical underventilation)
Marked obesity
DDX metabolic alkalosis
Hypochloremic alkalosis: loop/thiazide diuretics, vomiting, iatrogenic (sodium bicarb)
Concurrent alkalosis: pure water loss, hypotonic fluid loss
Chloride resistant alkalosis: HAC, hyperaldosteronism
Hypoalbuminemic alkalosis: PLE, PLN, liver failure
DDX respiratory alkalosis
Hypoxemia - stimulation of peripheral chemoreceptors
Non-hypoxemic activation of pulmonary stretch/nocireceptors: pulmonary embolism, fibrosis, edema
Fear, pain, anxietty
Spesis
fever
activation of central resp center – hyperventilation
