Renal/end/acid-base Flashcards
Classification of hormones
- Protein/peptide: ACTH, CRH, insulin
- Synthesized as prehormones
- Composed of amino acids
- Receptors on cell membrane - Steroid Hormone (aldosterone, cortisole)
- Synthesized from cortisol
- Lipid soluble
- Receptors in cytoplasm - Tyrosine Derived Hormones
- Catecholamines & thyroid hormones
2 phases of liver metabolism
Phase I: Hydroxylation/oxidation
Phase II: Glycuronidation/sulfation
Intracellular signaling with G coupled protein receptors
Adenyl CYclase –>cAMP–> PKA & phosphorylation of proteins
Phospholipase C –> IP3/DA –> protein kinase C resulting in phosphorylation IP3 –> increased intracellular calcium
Hypothalamus Control of pituitary
Anterior: neuroendocrine control of anterior pituitary
Posterior: Release neuropeptides in hypothalamic neurons
ADH secretion
Increased with: hypovolemia, decreased BP, nausea, pain, stress, barbiturates, morphine, nicotine, pther drugs
Decreased with: hypervolemia, hypertension, alcohol
What neuropeptides synthesized in parvocellular neurons
Anterior hypothalamus –> anterior pituitary
- CRH
- TRH
- GnRH
- GHRH (growth)
- Dopamine
Hormones from posterior pituitary
ADH
Oxytocin
Via magnocellular neurons
Different aquaporin receptors
AQP1: 90% receptors
- Luminal surface of thin LOH & proximal tubules
AQP2: only one that requires ADH - collecting duct
AQP 3& 4: basolateral membrane
Body management of oamolality
- Changed osmotic pressure sensed by hypothalamus osmoreceptors: subfornical organ, median preoptic nucleus & OVLT
- INcreased osmol –> cells shrink –> ADH release
- Decreased osmol –> cell swelling -> decreased ADH
*Sensitive to 1-2% change in osmolality
Biologic effects of thyroid hormones
- Receptors in all tissues
CV: inotropic/chronotropic
Bone: Growth
Liver: cholesterol metabolism
Calcium functions
- Coagulation
- Intracellular signaling
- 2nd messenger system
- action potential generation
- Neuronal transmission
- Bone structure
What factors control PTH release
- Calcium
- Phosphorus
- Magnesium
- Vitamin D
- Beta stimulation (increased PTH)
Renal effects of PTH
- Increased insertion of calcium channels on apical membranes of distal tubules
- increased calbindin –> facilitates diffusion into cell
- Increased calcium movement through basolateral membrane (calcium ATPase & Na-Ca exchange)
- Increased 1alpha hydrolase –> activates vitamin D
- Decreased Na-PO4 cotransporter at proximal tubule
PTH effect on bone
- Extracellular matrix
- Osteoblasts express PTH receptor –> increase proliferation
- Activation of osteoclasts:ruffled border in folding plasma membrane
Resorbs bone
3 fractions of calcium
50% iCa
40% protein bound
10% complexed
Cellular effects of vitamin D
- Bind cellular steroid receptors in target tissue
Target Tissue: Bone, kidney, intestines
Function of calcitonin
- Decreases Calcium!!
-Decreases bone resorption
-Inhibit osteoclasts
-Increase calcium excretion
Zona glomerulosa
- outer most layer
- Lacks 17alpha hydroxylase
- Aldosterone synthesis!!
Metabolism of glucocorticoids
- Lipophilic –bound to carrier proteins
- Transcortin
- Albumin
- Cortisol bindling globulin - Diffuse intracellularly binding to cytosolic receptors
- Elimination:
- Liver: biotransformation - conjugation –> excretion
- Localized tissue metabolism
Describe synthesis release of mineralocorticoids
- Synthesis & release regulated by:
- AngioII
- RAAS stimulation
- ACTH
- Hyperkalemia - Metabolism
- Liver/renal excretion
Made from cholesterol
Functions/effects of mineralocorticoids
- Regulate Na/K/H2O
- Receptors in distal tubule/collecting duct
- Principal cells
- inc transepithelial Na
- Inc apical Na channels
- Inc basolateral Na/K ATPase
- Inc H-ATPase (inc H excretion)
- Inc HCO3-Cl exchange
Adrenal medulla
- SNS ganglion
- Release of Ach bind chromaffin cells–> catecholamine release
**Very vascular
Catecholamine degraded by
COMT & MAO
**Break down into metanepherine and normetanephrine
Alpha and Beta effects
Alpha: Vasoconstriction, bladder sphincter contraction, bronchoconstriction, increased hepatic glucose production, decreased insulin, cardiac contractility, iris dilation, intestinal relaxation, pilomotor contraction
Beta: vasodilation, bladder relax, bronchodilation, glycogenolysis, increased glucagon, increased inotropy, lipolysis, increased renin
Pathophysiology hepatic encephalopathy
Inc NH3 + inc BBB permeability –> NH3 decreases excitatory neurotransmitters (NMDA, Cl postynapsis)
NH3 removed by transamination of glutamate into glutamine in astrocytes –> Glutamine exchange across BBB for tryptophan, serotonin & quinolate AND glutamine converted to glutamate –> overstimulated NMDA receptors
-Increases GABA tone–> due to increased NH4 & Mg –> inc peripheral type benzo receptors –> increased synthesis neuro steroids–> act on GABA
Granulomatous liver infections
Mycobacteria
Leishmania
Bartonella
Migrating nematodes
Biliary parasites
Platynosum concinnum
Amphimerus pseudofelineus
TX praziquantal
DDX infectious chronic hepatitis
RIckettsia
Salmonella Sp
Clostridium Sp
Campylobacter jejuni
Yersinia pseudotuberculosis
DDX acute hepatitis in dogs
Infectious: CAV-1 (adenovirus), lepto, clostridium, E.canis, herpes
Drugs: carprofen, acetaminophen, TMS, azathioprine, amioderone, mitotane
Idiopathic
Toxin: mycotoxin, cyanobacteria (blue-green algea), amanita, xylitol, alpha lipoic acid (human OTC antioxi), organic solvents (CCl4 - kill insects in grain)
MC biliary infections
Bacteriodes
Streptococcus
E.coli – emphysema may be present
Enterococcus
Clostridium - emphysema may be present
Helicobacter canis
Decrease phosphorus and RBC
Decreased CO2 –> shift of CO2 from intracellular to extracellular space –> increased intracellular pH –> increased use phosphate to phosphorylate glu –> RBC hemolysis
Tryptophan MOA in hepatic encephalopathy
- Directly neurotoxic
- increased serotonin: NMDA inhibition
- Increased Quinolic acid: NMDA excitation
Mechanism of Hepatic enceph NH4
- NH3 transamination to glutamine in astrocytes –> increases tryptophan in brain
- Inc excitability (over stimulate NMDA with help of glutamine)
- Dec excitability (inhibits Cl- extrusion from post synaptic cell; down regulate NMDA receptors)
- Brain edema
- Decreased microsomal Na/K ATPase in brain
Short chain fatty acids & hepatic encephalopathy MOAs
- Displaces tryptophan from albumin–> increase free tryptophan
GABA MOA in hepatic encephalopathy
- unclear if increased GABnergic tone
- NH3 & Mg increase expression of peripheral type benzo receptors
- increased neurosteroids bind and increase GABA activity peripherally
Glutamine MOA hepatic encephalopathy
- Alters BBB amino acid transport: Increased Trypotophan exchange –> increases serotonin and quinolate in brain
- Glutamine transported from astrocytes to neurons –> convert to glutamate–> overstimulates NMDA receptors (increased excitation)
- May cause increased osmolality of neurons –> cell swelling
Excess compounds with HE
- NH4: increased glutamine -
- Endogenous benzos receptors
- Neurosteroids
- Glutamine
- Aromatic amino acids
- Short chain fatty acids (inc tryptophan)
- Tryptophan
- Increased manganese
FAlse neurotranmitters in Hep Enceph & MOA
- Tyrosine –> Octapamine
- Phenylalanine –> phenylethylamine
- Methionine –> mercaptans
- inhibit/impair NE action
- Synergistic with NH4 & SCFA
- Dec NH4 detox in brain urea cycle
- Dec microsomal Na/K ATPase
MOA HE aromatic amino acids
- Normally balanced by nonaromatic AA
- Leads to increased production of false neurotransmitters & decreased dopamine & norepinephrine –> coma
MC bacteria pyometra
- MC ecoli
-strep
-enterobacter
-proteus
-klebsiella
-pseudomonas
4 phases AKI
- Initiation: subcellular injury
- Extension: cellular injury –> death –> biochemical derangements & clinical manifestation of disease
- maintenance: Cell death & regeneration simultaneously –> poss recovery determined by balance between 2
- Recovery: Improved GFR & tubular function ** may last weeks to months**
UOP categories
Anuric - none
Oliguric (<0.5 ml/kg/hr)
polyuric (>2 ml/kg/hr)
** Fluid overload >10% baseline body weight
Causes of Resp Acidosis
** Increased CO2 production or decreased minute ventilation**
-Pulm/small airway disease
- Resp center depression
- NM disease
- Restrictive extrapulmonary disorders
- Large Airway obstruction
- Marked Obesity
- Ineffective mechanical ventilation
- INc CO2 product( hyperthermia, seizures, fever, malignant hyperthermia)
Causes of respiratory alkalosis
- Iatrogenic (mechanical vent)
- Hypoxemia –> stim increased minute ventilation
- Severe Pulmonary disease
- centrally mediated hyperventilation
- Pain, fear, anxiety
Normochloremic metabolic acidosis
- has increased anion gap (may be inapp elevated if hyperalbuminemia)
- DUEL
- DKA
- Uremia
- Ethylene glycol
- Lactic acidosis
- Other/less common:
D-lactic acidosis
Salicylate ingestion
methanol intoxication
Expected compensatory changes in met acidosis
Met acidosis
- dec pCO2 0.7 mmHG –> 1 mEq/L dec in [HCO3] +/-3
Met alkalosis
- Inc pCO2 of 0.7 mmhg –> 1 mEq/L decrease in HCO3 +/- 3
Causes of metabolic alkalosis
Cl responsive
- vomiting
- diuretics
- correction of resp acidosis
Cl resistant
- primary hyperaldosteronism
- Cushings
- Over administration of alkaline fluids
Hyperchloremic metabolic acidosis causes
- GI loss –> loss Na relative to Cl (bicarb loss)
- Renal bicarb loss
- Hypoadrenocorticism
- NaCl adminmistration
- Renal tubular acidosis
Oliguria
UOP less than noraml ( dogs <0.27 ml/kf/hr)
- Hydrated, well perfused pt: <1 ml/kg/hr = absolute oliguria
- Pt with IVF UOP 1-2 ml/kg/hr = relative oliguria
- Prerenal oliguria: urine [Na] <20 mEq/L
Prerenal causes polyuria
- increased intake : psychogenic OD, IVF
- Drugs: diuretics, alpha2 agonists, K agonist, alcohols, steroids, anticonvulsents
- Hormonal: hyper/poadrenocortiscism, diabetes insipidis, increased T4, cerebral salt wasting syndrome
- Electrolytes: low K, HIgh Ca
- Osmotic: diabetes, salt ingestion, glycols, e.coli endotoxin, liver disease
Postrenal polyuria
Post obstructive diuresis
- Likely due to proximal tubule dysfunction, altered ADH responsiveness & osmotic diuresis
**Tx aggressive IVF
Insensible losses
Cannot be measured
-Evaporation can be 20-70 ml/kg/day depending on activity of patient
Catheter assd bactiuria
Asceptically obtained urine from indwelling catheter within 48 hrs of removal of cath that tests + for species of bacteria at 10^5 CFU/ml
Body’s processes to maintain acid base
- regulation PCO2 by ventilation
- Buffering of acids with bicarb, PO4, and proteins
- Changes in renal excretion of acid or base
2 mechanisms metabolic acidosis
- Bicarb loss(Cl- gain)
- GI loss
- renal loss –> appropriate response or renal tubular acidosis
- Admin NaCl
2.Acid gain
- DUEL
-Salicylate ingestion (aspirin)
- methanol intoxication
4 mechanisms extracorporeal therapy
- diffusion –> small & some medium MW solutes move easily. Charges have some effect (dialysate has physiologic levels of things (Na, glu, k, ect )in plasma )
- Convection–>Flow of solutes by hydrostatic or osmotic gradients (water drags solutes with it)
- Removal small medium and large MW solutes - Ultrafiltration –> removing fluid (WATER) from blood via hydrostatic pressure (For FO)
- Adsorption: sticking to membrane (toxins, not huge thing in renal cases)
RAAS
- Decreased renal blood Q & Na to distal tubule → macula densa releases renin→ Renin converts Angiotensinogen (from liver) to Angiotensin I→ ACE converts Angio I to Angio II → aldosterone production→ renal Na and water retention, myocardial apoptosis, cardiac and vascular remodeling & fibrosis, increased thirst and vasoconstriction
- Local tissue RAAS is thought to encourage local cardiac remodeling
- Angio II can be generated from pathways independent of ACE → therefore can still have aldosterone and Angio II production with ACE inhibitors
- Aldosterone
What causes an increase in anion gap?
Ketones, lactate, uremia, methanol, ethylene glycol, metaldehyde
- Only reason for low AG is albumin low
Not useful in hypoalbuminemia
Renal Tubular Acidosis
Distal
Distal: Urine cannot be maximally acidified due to impaired H+ ion secretion in the collecting ducts
urine pH >6.0 despite markedly decreased plasma [HCO3]
Step 1: rule out ureases positive UTI ( Proteus sp., Staphylococcus aureus)
Step 2: Diagnosis is confirmed via ammonium chloride tolerance test during which urine pH is monitored before and after at hourly intervals for 5 hours after oral administration of 0.2 g/kg NH4Cl
Treatment potassium citrate
Often companied by hypOkalemia
- Causes: pyelonephritis, IMHA, addisons
Renal tubular Acidosis Proximal
Proximal: Renal reabsorption of HCO3 markedly reduced and urinary fractional excretion of HCO3 is increased (>15%) when HCO3 is increased to normal
- Diagnosis: acidic urine pH <5.5 or 6 in the presence of hyperchloremic metabolic acidosis and a normal GFR BUT after plasma HCO3 is normalized by akali administration, an increased urine pH (>6.0) and increased urinary fractional excretion of HCO3 (>15%)
- Next Step: Rule out Fanconi (add prox tubular dysfunction): glucouria despite normal BG
- Difficult to correct. As normalize blood HCO3, they excrete more
- Causes: fanconi syndrome, toxins, drugs, hypoparathyroidism, multiple myeloma
Adverse effects of metabolic acidosis
- Decreased myocardial contractility,
- Arterial vasodilation & venoconstriction
- Impaired coagulation
- increased work of breathing secondary to CO2 production
- Decreased renal and hepatic blood flow
- insulin resistance
- Altered central nervous function
Indications for Dialysis
- severe progressive azotemia (Crea >10 or anuria)
- Severe hyperkalemia NOT responding to medical management
- Life threatening FO (esp if oliguric or anuric)
- Severe acid base disturbances
- Uncontrolled uremia that is unresponsive or minimally responsive to traditional medical management (after 12-24 hours on IVF)
Contraindications Dialysis
Hemodialysis
- coagulopathy - especially when only heparin is availble and not regional citrate
- Severe hypotension
Peritoneal dialysis
- peritonitis
- recent abdominal or thoracic surgery
- Hypoalbuminemia
- Severe hypercatabolic states
Different extracoporeal types (intoxications)
- Hemofiltration: works by diffusion –> effective with small (<500-1000Da), water soluble solutes with low protein binding (<80%)
- Hemofeiltratoin/hemodiafiltration: works by convection; better for larger solutes (1000-10x Da)
- Hemoperfusion: works via adsorption; large particles (>10K da) or with high protein binding (>95%)
- Plasmapharesis: works via centrifugation; good for large (>50x Da) or highly protein bound (>95%) that are in plasma compartment
Causes of acquired CENTRAL diabetes insipidis
- Brain trauma
- Neoplasia (intracranial or lymphoma)
- INfectious/inflamm (meningitis, encephalitis, toxo, histiocytosis, crypto)
- Vascular (hypothalmic infarction, intracranial hemorrhage or hypoxic enceph)
- Immune mediated
- Idiopathic
Causes of acquired NEPHROGENIC diabetes insipidis
- Drugs (vasopressin, ofloxcin, ampho B, aminoglycosides, cisplatin, vinblastine, colchicine)
- Electrolyte abnormalities (hypercalcemia, hypokalemia)
- Bacteria (E. Coli, Streptococcus, lepto) –> pyo, pyelo, SEPSIS
- Degenerative (CKD, amyloidosis)
- Paraneoplastic (Intestinal leiomyosarcoma)
- Addisons
- Liver insufficiency/ PSS
Causes SI ADH
- CNS disease
- bleeding mass or lesion (hydrocephalus)
- infection (meningitis)
- Other (TBI in human, liver disease) - Pulmonary Disease
- Pneumonia
- PPV in humans - Drugs
- Vinca alkaloids
human med:
- PPIs
- SSRIs
- Opiates - Idiopathic
- Immune mediated Disease
Diagnostic Criteria of SI ADH
- hypoosmolar hyponatremia*
- euvolemia
- Inappropriately concentrated urine (U osm >100 mOsm/L)*
- Urine Na concentration >30 mmol/L
- Hypoadrenocorticism excluded
- *If not able to check immediate osmolality : USG >1014 expected, but USG >1005 suggestive of Uosm >100**
Clinical signs of thyroid storm
- CNS disturbances (msot commn in feline pts)
- HypERthermia (often not present in felines)
- Acute vomiting or diarrhea
- Abdominal pain
- Extreme muscle weakness & cervical ventroflexion
- Icterus
- Cardiac murmurs +/- arrhythmias
- Pleural effusion
- Pulmonary edema
- Tachypnea
- Hypertension
- Retinopathies
- Thromboembolic disease
- Sudden death
** Human Med muhave 4 major signs:
1. CNS signs
2. GI and hepatic dysfunction
3. Fever
4. Cardiovasc signs**
Drugs to avoid with pheochromocytoma
- Metoclopramide
- Histamine
- Tyramine
- Glucagon
- Anticholinergics –> preop avoid (ace, atropine), inc SNS
- Barbituates –> vent arrhyth, inc SNS
- Halothane - sensitizes myocardium to catecholamines
- Long acting beta blockers –> loss B2 vasodilation may worsen hypertension
Hepatorenal Syndrome
Rare in VM
Diagnosis DI
Consider if:
- USG 1001-1007 (complete)
- USG 1015-1018 (Partial)
Diagnosis requires:
- rule out of toher diseases
- Measurement water consumption (>100 ml/kg/day), measurement UOP (>50 ml/kg/day) & USG </= 1012
- Normal UA/u culture
- AUS, XR
- IF all above normal, modified water deprivatoin test (must r/o psychogenic or primary polydypsea)
