Exam 3 Flashcards
Laboratory evaluation of the Hepatobiliary System and Skeletal Muscle disorders 1
Indicators of Hepatocellular Damage
What are the Biomarker enzymes of tissue injury in vetmed?
What are the different half lives?
Which ones apply mostly to small, large, or exotic animals?
Which is high in cats with hyperthyroidism?
Which ones also from cardiac muscle and RBCs?
- Leakage enzymes
-Biomarkers of tissue injury
-Magnitude usually reflects the severity
Types of damage/injury
-Hypoxia
-Toxins
-Inflammation: usually chronic in dogs
-Metabolic: Cushing’s disease
-Neoplastic: biliary tumors in cats
-Trauma
-Half life of enzyme can lead to inability to detect in blood and less abundance in test results
- Etiologies of leakage enzyme elevation
- General Enzyme Interpretation
Hepatic origin biomarkers of tissue injury
- ALT: small animal mostly
-Alanine transaminase: Cytosolic enzyme
-Tissue sources: hepatocytes and skeletal muscle
-Half like: cats 3.5 hrs, dogs 2-3 days.
-Generally specific indicator of hepatocellular injury in small animals
-Serum levels rise within 12 hrs, peak 1-2 days after injury
-ALT = Liver True
-Mild increase in severe myopathies and feline hyperthyroidism - AST: Small and large animal
-Aspartate transaminase: cytosolic, mitochondrial
-Tissue sources: hepatocytes, skeletal, cardiac mm, RBCs.
-Relevant species and half lives: all species; cats 1.5 hrs, dogs and cattle <1day, horses 8-8 days.
-Clinical application: raises differentials of hepatocellular injury, muscle injury, intravascular or in vitro hemolysis, and delayed serum separation.
-Often normalizes prior to ALT with resolution of hepatic injury.
-Small animals: evaluate with CK to determine tissue of origin
-AST: “Sort of True”
-Rough venipuncture or delayed serum separation commonly cause a minor increase. - SDH: Large animal
-Sorbitol dehydrogenase: cytosolic
-Hepatocytes and other tissues
-All species, but especially large animals.
-Cats 3-4 hrs, dogs 4 hours, horses 12 hours
-Sensitivity and specific indicator of hepatocellular injury in domestic species.
-Elevates within 12-14 hours and returns to normal within 2-3 days.
-Best to run alongside AST, and if possible, GDH to strengthen dx. - GDH: Large animal
Not available in US
-Glutamate dehydrogenase: mitochondrial, irreversible damage
-Hepatocytes and other tissues such as kidney and GI in minor activity
-All species, but especially large animal and exotics.
-Dogs 8 hours, horses and cattle 14 hours.
-Sensitive and specific indicator of hepatocellular injury in all species. - LDH: exotics, large animal, mixture
-Lactate dehydrogenase
-Hepatocytes, cardiac and skeletal muscle, RBCs.
-All species
-May help refine diagnosis of hepatocellular injury, muscular injury, or hemolysis.
-Inexplicable elevations of great magnitude may occur.
-Total LDH includes 5 isoenzymes present in varying amounts, electrophoresis may differentiate.
-It does not confer additional information to AST
Etiologies of Leakage Enzyme elevation (FYI)
-Aflatoxin
-Amanita mushroom
-Arsenic compounds
-Blue-green algae
-Copper
-Herbicides
-Insecticides
-Iron
-Sago palm
-Xylitol
-Zinc
Large animal specific
-Cocklebur
-Fumonisins
-Fusarium (equine)
-Mycotoxic lupinosis (ruminants)
-Panicum grasses
-Pyrrolizine alkaloids
Copper Toxicity
Bedlington Terrier dogs and Sheep
-Gold Standard diagnosis: liver biopsy for dry weight copper measurement
-May be associated with acute or chronic hepatitis in dogs
-Special stains (rhodamine, rubric acid)
Sago palm toxicity
-Severely hepatotoxic in all domestic species
-All parts of the plant are toxic
-Severity is dose dependent
-Hepatic necrosis may occur acutely
Active Cirrhosis
Feline hyperthyroidism
Hepatic parasites: fasciola hepatica, Heterobilharzia americana
Hypoxia
Neoplasia
Theiler’s disease (equine)
Trauma
Tyzzer’s disease (rodents, NAVLE)
General Enzyme interpretation guidelines
-Tissue correlation with disease vary by enzyme and species
-Enzymatic assays may be performed differently between labs, therefore RIs (reference intervals) are not interchangeable.
a. Short enzyme half-life
b. End stages of tissue damage
c. Chronic smoldering disease process
**> or = 2-3 times upper reference limit (URL) is considered significant
**Severity: 2-3 times URL = mild
**4-5 times moderate threshold
**> 10 times marked (may see > 100 times)
-Values less than the lower reference limit are considered insignificant
*Critical to trend values over time
-A single, mildly elevated analyze may be non-specific and insufficient for the diagnosis of hepatobiliary disease
Indicators of Cholestasis
A. Inducible enzymes
-Transcription induced by stimuli
-Indicators of obstructive cholestasis
-Intrahepatic: hepatocyte swelling, inflammation, neoplasia.
-Extrahepatic: bile duct obstruction, gall bladder rupture, pancreatitis, neoplasia.
ALP
-Alkaline Phosphatase: cell membranes
-hepatocytes (L-ALP), osteoblasts (B-ALP), intestine, kidney, mammary glands, placenta.
-Dogs, cats, large animals.
-Clinical applications: cholestasis, steroid induction (C-ALP dogs only), suckling or growing animals, osteoblast proliferation (hyper plastic or neoplastic), drug induced.
In cats helpful for detecting hepatic lipidosis, otherwise insensitive
**Steroid induction in dogs may be due to endogenous (Cushing’s) or exogenous corticosteroids.
-Cholestasis induces ative transcription of L-APL, with increased sinusoidal location.
GGT
-Gamma glutamyltransferase (GGT): cell membranes
-Biliary epithelial cells, pancreatic acing cells, renal tubular epithelial cells, mammary, all other membranes
-All species, dogs, and horses (t 1/2 = 3 days)
-Cholestasis, biliary hyperplasia, indication of passive transfer (calves, puppies)
GGT more specific for cholestatis than ALP in all species, and more sensitive than ALP in cats and large animals.
-Also associated with right dorsal displacement of the large colon in horses. May identify acute renal tubular damage when run on urine.
Biliary Hyperplasia
-Commonly occurs in large animals ingesting pyrrolizidine alkaloids (PA) containing plants
CATS
-Increase in ALP > GTT = hepatic lipidosis
-Increase in GGT > ALP = cholangitis and or pancreatitis
Indicators of Cholestasis Continuation Led 32
B. +/- Hyperbilirubinemia
-Bilirubin is physiologically produced from the routine breakdown of RBCs by macrophages in the spleen and bone marrow.
-Initially bilirubin is unconjugated/indirect (think pre-fix = pre-fixed)
-Albumin acts as a cart to carry it to liver for conjugation (fixing it as water soluble); water soluble bilirubin is termed conjugated/direct
-Conjugated bilirubin travels via bile to the GI for further processing by bacteria. No longer bound to albumin
Pre-hepatic
-Extravascular hemolysis (IMHA, NI)
-Physiologic: hyporexic horses, neonates, hyperemic ruminants.
Hepatic
-Intrahepatic cholestasis
Post-hepatic
-Extrahepatic cholestasis
C. +/- Hypercholesterolemia
-Cholesterol is excreted in bile
-Cholestasis induces production of cholesterol-rich lipoproteins
D. Functional Cholestais
-Occurs without any physical obstruction or impairment of bile flow
-Decrease bile flow due to cytokine-mediated down regulation or inhibition of transporters responsible for excreting bile salts or conjugated bilirubin into bile
-Increase in bilirubin often with mild increase in hepatic leakage enzymes and little to no increase in inducible enzymes
-Has been associated with E. coli infections, potential indicator of sepsis
Bilirubin conjugation/ metabolism
Initially pre-hepatic, mostly unconjugated bilirubin
-Heme (Red) to Biliverdin (green) to Bilirubin (yellow)
Hepatic: mix of conjugated and unconjugated bilirubin
Hypercholesterol, Cholestasis
Hypercholesterolemia
Cholestasis will lead to hepatocellular damage and vice versa. We should strive to identify the primary process by identifying whether leakage or inducible enzymes are more severely increased
Biochemical indicators of Sepsis
-Hypoglycemia
-Hypocholesterolemia
-Hypocalcemia
-Hypomagnesemia
-Functional cholestasis
Assessment of Hepatic Function
What are some of the c/s for hyperammonemia?
What are some of the causes for bile acids increased levels in circulation?
What are the ABBCG levels of pseudo tests?
A. Hepatic function tests
-Hyperammonemia due to (~60%) dysfunction: hepatic urea cycle impaired. Systemic circulation increase of ammonia
-Hyperammonemia protosystemic shunt.
-Hepatic encephalopathy: neurological disease due to toxic effects of ammonia on the CNS. Dull mentation, loss of learned behaviors, change in demeanor. May be due to hepatic dysfunction or protosystemic shunt.
-Tests are tricky because samples need to be placed on ice immediately and shipped off. Available for most bench top analyzers
Bile metabolism
-90% reabsorbed via portal circulation
-Bile acid - PSS, reduced hepatic mass
-Large animals: single non-fasted sample
-Small animals: fasted, 2 hours post-feeding sample
-Bile acid - cholestasis
-Canalicular BA transport proteins are down regulated
-BA “regurgitated” into sinusoidal blood.
-Causes for elevated bile acids: porto systemic shunts (decrease hepatic clearance, decrease hepatic mass). Cholestasis (bile backs into sinusoids, then systemic circulation). Hepatic disease (reduced functional mass for enterohepatic resorption).
Elevated bile acids is very sensitive and specific for these conditions in dogs, cats, horses, and cattle
*Contradiction for BA PSS testing: cholestasis or GI malabsorption previously established
Protosystemic shunts pre-despised breeds
-Yorkies
-Young animals
-Small breed dogs often have a single extra hepatic shunts
-Large breed dogs often have a single intrahepatic shunts
-CATS nearly always have extra hepatic shunts
-Acquired/Secondary shunts develop secondary to hepatic hypertension. Occur at any age in any breed.
B. Pseudofunction tests
Biochemistry panel
-Albumin Decreased with Decreased systemic function (highly conserved)
-Bilirubin increased with decreased excretory function
-BUN decreased with decreased systemic function
-Cholesterol decreased with synthetic function
-Glucose decreased with synthetic function (may also be increased, not reliable)
Coagulation panel
-Prolonged prothrombin (PT), partial thromboplastin (PTT), Fibrinogen decreased with synthetic function
Review of biochemistry panels so far
Indicator of skeletal muscle damage, etiologies, indicators of cardiac muscle damage
Indicators of muscle damage
A. Indicators of skeletal muscle damage
Creatine Kinase (CK)
-All species
-Four isoenzymes: CK-1 (does not cross BBB), CK-2 (cardiac muscle), CK-3 (skeletal muscle) CK-Mt (mitochondria of many tissues).
-Very sensitive and specific for skeletal muscle damage.
-Half life 1-4 hours, will return to normal RI within days of a single insult
-Clinically significant increase are typically quite dramatic >20 times URL.
Aspartate Transaminase (AST)
Lactate Dehydrogenase (LDH)
Less Common: measurable release of ubiquitous intracellular analyses (K, Ca, Phos)
If muscle insult is severe enough: mild ALT increase
B. Etiologies of Skeletal Muscle Injury
-Trauma: HBC, IM injection, seizures, rough venipuncture
-Exertional rhabdomylosis (equine polysaccharide storage myopathy)
-Prolonged recumbency (large animals)
-Saddle thrombus (feline)
-Vitamin E or Selenium deficiency
-Myositis from infectious causes: toxoplasmosis, neosporosis, bacteria, etc.
-Inherited diseases: hyperkalemic myopathy, muscular dystrophy
-Toxin ingestion: gossypol, monensin, castor bean
-Neoplasia
Levels
-Myoglobinuria and myoglobinemia
-CK increased
-Lactate increased
-AST increased
Complications of Rhabdomylysis
-DIC (late). Thromboplastin release and thrombotic microangiopathy. Tx: fresh frozen plasma
-Hyperkalemia: Potassium release from damage muscles and decreased clearance from acute kidney injury. Tx: IV fluids, diuresis, Calcium gluconate, etc.
-Hyperphosphatemia: muscle breakdown. Tx: diuresis, hemodialysis.
-Acute kidney injury: direct effect of myoglobin +/- hypovolemia. Tx: IV fluids, bicarbonate, hemodialysis.
-Compartment syndrome: muscle ischemia, fluid sequestration. Tx: Fasciotomy
-Hypovolemia: from sequestration of fluids in the muscles. Tx: IV fluids.
-Hypercalcemia: efflux from damaged muscles and slow clearance. Tx: Iv fluids, diuresis.
C. Indicators of cardiac muscle injury
-Natriuretic peptides: a measure of cardiac “stretch”
-N-terminal pro B-type natriuretic peptide (NT-pro-BNP), most commonly used
-Atrial natriuretic peptide (ANP) more biologically active but less stable
-Increase proportionately with disease progression
-Endothelin-1
-Cardiac troponin I (cTnI): less sensitive, released after cardiomyocyte death.
Increased BNP is highly sensitive for detection of occult dilated cardiomyopathy (detects DCM prior to development of congestive heart failure)
-NT-pro-BNP is cleaved from BNP in response to increased cardiac filling pressure (myocardial stretch) and ischemia.
-NT-pro-BNP has greater stability and a longer half life than other cardia biomarkers. May help differentiate cardiac disease from primary respiratory disease
Cardiac biomarkers should always be interpreted in light of other cardiac assessment: ECG, electrocardiogram, and thoracic radiographs
Laboratory evaluation of Exocrine Pancreas and GI tract
Endocrine
-Islets of Langerhans cells
-Secrete hormones into blood vessels
Exocrine
-Acinar cells
-Secrete digestive enzymes into pancreatic duct
Exocrine Pancreatic & GI Function
Which cells decrease a mixture of active and inactive digestive enzymes?
Which part/cells secrete bicarbonate?
What is the sequence of the flow of secretion?
Where does the activation of proteases occur?
What enzyme hydrolyses carbohydrates into disaccharides?
A. Exocrine Pancreas
Acinar cells contain Zygomen granules
-Proteases (all zymogens)
-Lipases
-Pancreatic amylase
-Nucleases (ribs and deoxyribonucleases)
Pancreatic ductular epithelial cells secrete bicarbonate
-Enzymes, zymogen, and bicarbonate exists in aqueous solution
Flow of secretion
-Interlobular ducts
-Pancreatic ducts
-Duedenum
Proteases Activation occurs in duodenum
-Enterokinase initiates conversion of trypsinogen to trypsin
-Trypsin activates all three
-Breaks proteins down to peptides, then HAs, eventually acted upon by bacteria (ammonia - hepatic urea cycle - UN).
Lipases
-Pancreatic lipase
-Cholesterol esterase (non-specific lipase)
-Phospholipase
-Procolipase (zymogen)
Lipid absorption and digestion is aid by bile acids
Amylase
-Hydrolyzes most carbohydrates into disaccharides and some trisaccharides
-Some species have salivary amylase
B. Gastrointestinal tract
-Control of gastric, biliary, and pancreatic secretions: G-cells enteroendocrine cells of the pyloric antrum and duodenum that release gastrin which functions are:
-Gastrin: Parietal cells = HCL
-Gastrin: Chief cells = pepsinogen
-Gastrin: stimulates secretion of pancreatic enzymes
-Surface area for absorption of nutrients and water
-Environment for symbiotic (and some opportunistic) bacteria
-Peristalsis
-Mucus production
-Immune surveillance
Gastrin
Parietal cells
Chief cells
S cells
I cells
Control of biliary secretions
-I cells: enteroendocrine cells of the duodenum and jejunum that release Cholecystokinin (CCK)
-CCK release is triggered by partially digested proteins and fats in the small intestine
CCK functions:
-Stimulates contraction of the gallbladder
-Increase bile production
-Stimulates secretion of bile salts
-Stimulates secretion of pancreatic enzymes
-S cells: enteroendocrine cells of the duodenum and jejunum that release secretin
Secretion functions:
-Release is triggered by pH drop pf 4 or less
-Secretin stimulates the release of large quantities of water and bicarbonate to protect the intestinal lumen
Nutrient absorption
-Foliate: SA
-Cobalamin: SA
-Glucose: LA
-Lactose: LA
Evaluation of exocrine pancreatic disorders
What is the gold standard test?
What are the RI values that indicate EPI or resets needed?
A. Pancreatitis
-Inflammation of the pancreas
-Acute very common in dogs
-Chronic more common in cats
-Largely effects the exocrine pancreas: 90% reduction of functional pancreatic mass leads to exocrine pancreatic insufficiency
-Diabetes mellitus has been shown to precede development of EPI in dogs and people.
Routine blood work may include amylase and lipase, but they are produce by many tissues other than the pancreas. Poor sensitivity, poor specificity
Evaluation
Ultrasound findings may help:
-hypo echoic areas within the pancreas (possibly indicating necrosis or fluid accumulation). Increased echogenicity of the surrounding mesentery (due to necrosis of the pancreatic fat, which becomes mineralized)
-Enlargement and/or irregularity of the pancreas
-Dilation of the pancreatic or biliary duct
-Abdominal effusion
SNAP cPL
-In house testing, 95% agreement with Spec cPL
-91-94% Sn negative rules out pancreatitis
-71-78% Sp may detect “gray zone” positives retest
Spec cPL/fPL
-Considered the most specific serum tests of pancreatitis
-Send out testing (IDEXX)
-cPL: 72-78% Sn, 81-100% Sp. RI: 0-200 ug/L 201-399>/= 400 positive
-f/PL: 79% Sn, 67-100% Sp. RI: 0-3.5 ug/L >= 5.4 positive
B. Exocrine Pancreatic Insufficiency
-Pancreatic acing atrophy recognized in dogs, juvenile onset.
-German Shepherds and Roughed coated Collies predisposed/common. Autosomal recessive inheritance.
-Proposed mechanism: immune-mediated
-Expensive to treat
Evaluation
Serum trypsin-like immunoreactivity (TLI) is the gold standard
-Collect fasted sample; ship at ambient temp.
-Texan veterinary labs
-Dogs: TLI <2.5 = EPI, 3.5-5.7 retest in one month
-Cats: TLI <8.0 = EPI, 8.0-12 retest in one month
Evaluation of GI disorders
What bacteria induces lactase deficiency in foals leading to maldigestion?
What is the normally expected increase in RI for the oral glucose absorption test?
A. Maldigestion and Malabsorption
-Maldigestion: EPI, bile salt deficiency, defect in luminal microflora
-Malabsorption: mucosal abnormality, lymphatic obstruction, digestive defect.
Folate
-Performed in companion animals
-Folate is absorbed selectively by the proximal small intestines
-Duodenum and proximal jejunum
-Below RI = proximal intestinal mucosal disease or all cheese diet
-Above RI = Increased intestinal absorption. Ex: Proximal intestinal bacterial overgrowth. Decrease intestinal pH (EPI, excessive gastric acid secretion). Dietary supplementation, Feline cobalamin deficiency hemolysis.
Cobalamin
-Absorbed selectively in the ileum
-Below RI = ileal absorption problem. Ileal disease or resection - commonly. Inflammatory bowel disease, Villous atrophy. Pre-absorptive less common. EPI or intestinal bacterial overgrowth.
-Above RI: uncommon, no known significance
Cobalt
-Deficiency in cattle and sheep
Oral glucose absorption test
-Performed in horses with chronic weight loss, cow-pie feces. Signs of LI disease
-Equids: carbohydrates absorbed and digested in LI.
-Glucose given orally via stomach tube. Trend blood glucose
-Blood glucose increases to reflect amount absorbed.
-2 hrs post-administration: blood glucose should be 158-200% of the baseline value
-Decrease reflects malabsorption (ddx prolonged transit time, delayed gastric emptying)
Lactose Tolerance Test
-Performed in foals to assess lactase activity (digest lactose)
-Rotavirus and Clostridium difficile enterocolitis induce lactase deficiency, which causes maldigestion
-Lactose given orally via stomach tube
-Blood glucose increases
-Adequate lactase activity: Blood glucose 150-200% baseline at 60-90 minutes out
-Peak glucose at least 35 mg/dl above baseline
-Inadequacy suggests infectious maldigestive process
Gastrointestinal Hemorrhage Evaluation
-Blood acts as a protein-rich meal
-Gastric and upper intestinal hemorrhage will increase BUN
-Concurrent NSAIDs and steroid use
-Excess acid production: gastrinoma (Zollinger-Ellison syndrome)
Miscellaneous information on proteins
What proteins test indicates PLE when found in feces?
C. Protein Losing Enteropathy
Causes
-Lymphoplasmacytic enteritis has recently been recognized as a leading cause
-Lymphangiectasia
-GI neoplasia (LSA primarily) Lymphoma
Routine serum biochemistry
-Panhypoproteinamia: decrease Albumin, decrease Globulins, decrease Cholesterol.
Auxiliary testing
-Fecal alpha-1 inhibitor concentration: send out for test on dogs (TAMU). Physiologically found in plasma, NOT feces.
-Presence in feces indicates leaching from the intestine (PLE)
Miscellaneous information on proteins
A. Globulin
-Calculated value on routine serum biochemistry panels
-Globulins = Total Protein - Albumin
-Mostly made by the liver except B-lymphocytes and plasma cells.
Gammopathies
-Monoclonal: Immunoglobulin-secreting B-lymphocytic or plasma cell neoplasm
-Polyclonal: Antigenic stimulation
-Possible sequel: Hyperviccosity syndrome. AL amyloidosis
Analyze and value examples
- Dehydration: (hemoconcentration, elevated albumin (due to ECF loss), may also detect decrease GFR (Increase BUN, Cream, MG, +/- Phos).
-TP increase
-ALB increase
-Glob increase
- Acute Phase Protein inflammation: Albumin is negative acute phase protein. Nearly all globulins are positive acute phase proteins. Protein production shifts (defense mechanism). TP may occasionally be mildly increased. Increase WBC may or not accompany.
-TP: WRI
-ALB: Decrease
-GLOB: Increase
- Protein losing enteropathy: reflects glomerulopathy (glomerulonephritis, amyloidosis). May rarely be severe enough to decrease globulins. If cholesterol is increased mechanism is unknown and edema formation occurs, consistent with nephrotic syndrome
-TP: Decrease
-ALB: decrease
-GLOB: WRI
- Protein losing enteropathy: Panhypoproteinemia usually with hypocholesterolemia. HCT WRI, unless concurrent with hemorrhage.
-TP: decrease
-ALB: decrease
-GLOB: decrease
-Chol: decrease
-HCT: WRI
- Hemorrhage: most consistent with external blood loss, as protein resorption occurs to some degree with internal blood loss. Check MCHC and reticulocyte count to determine iron status and chronicity
-Everything decreased
- Multiple possibilities: antigenic stimulation (increase if chronic) vs. neoplasm (usually increase), increasing globulins. Acute phase response with hypoalbuminemia masked by dehydration (very common, check for decrease GFR).
-TP: increase
-ALB: WRI
-GLOB: increase
- Note on Albumin: Albumin is the major carrier molecule of the blood. When decreased, the albumin-bound fractions of divalent cations will be decreased. Decreased Albumin accounts for mild reduction in total calcium and total magnesium
Acute Phase Proteins
-Markedly high with inflammation
-Dogs: C-reactive protein, Serum Amyloid A
-Cats: Serum Amyloid A
-Horses: Serum Amyloid A
-Cattle: Haptoglobin, Serum Amyloid A
-Pigs: C-reactive protein, Major Acute Phase Proteins, Serum Amyloid A.
Hepcidin causes iron to be sequestered in enterocytes, reducing bioavailability to infectious organisms
Urinalysis 1`
- Interpret urinalysis results and assess possible disease development Click to add subtitle
- Discuss potential causes of glucosuria, ketonuria, bilirubinuria, and
Learning Objectives
proteinuria - Discuss potential causes of hematuria and pyuria
- Recognize cells and structures commonly identified on urine sedimen exam from healthy and diseased domestic animals
Urine collection and physical properties
Collection methods
Free catch: inherently non-sterile
-Mid-stream collection preferred
-Ensure container is labeled
-Wear gloves (leptospirosis?)
-Difficult: Oliguric patients, incontinent, obstructed, behaviorally challenged, etc.
-Be cautious with manual bladder expression: stones, rapture ladder, pain.
Urethral catheterization
-Sterile
-Aseptically prepared
-Can collect even when little urine present
-Must be performed by trained personnel.
-Sedation required in cats
-Female dogs, challenging
-Risks: iatrogenic UTI, hemorrhage, perforations
Cystocentesis
-Most sterile
-Best for culture (fill culture tube first)
-Sedation typically not needed
-Bladder needs to be somewhat filled
-Same risks as above.
-Trained personnel
Physical Properties
Gross appearance
Concentration
-Pale yellow: dilute
-Yellow to amber: concentrated
-Dark yellow/yellow-brown: very concentrated
-Correlation: dehydrated patient with diluted urine would be a concern
Turbidity
-Cloudiness = particular matter: cells, crystals, amorphous debris, lipid, mucus, organisms, feces.
-Increased turbidity should trigger a sediment exam.
-Exception horses: physiological mucoprotein
Color
-Affected by: disease, diet, drugs, environment.
-Aberrations: termed pigmenturia, red (various hues), brown.
-Green: uncommon
Red-brown etiologies
-Hematuria (occult blood positive)
-Hemoglobinuria (occult blood positive)
-Myoglobinuria (occult blood positive)
-Bilirubinuria (occult blood negative, bile positive)
Points of differentiation
-Centrifuge: Red pellets = hematuria
-Hemolyzed plasma indicated hemoglo binemia, suggests potential for hemoglobinuria. BS in dogs, RBC ghosts
-Serum biochemistry Increased CK and AST = myoglobin
Bracken fern
-Hematuria in cattle
-Induces urinary hemangiosarcoma
-Consider enzootic hematuria induced by bracken fern grazing over a period of months
-Retinal degeneration and blindness in sheep
-Thiamin deficiency in horses: blindness, depression, weight loss, anemia.
-General neoplasia in all species.
-GI and renal tumors observed
-Young fiddleheads most carcinogenic
Bacillary hemoglobinuria (red water)
-Clostridium hemolytic induces hemolysis, exceeds capacity of haptoglobin and causes “port wine” urine
-Pathogenesis is potentiated by liver fluke Fasciola hepatica, creates the required anaerobic conditions in the liver
Refractometric USG
-Estimation of urine osmolarity based on refraction of light
-Hard measure of urine concentration
-Necessary for classification of Azotemia
-Manual and digital refractometers available
Urine sediment: crystals and casts
A. Urolith-Forming Crystals
Struvite - triple phosphate
-Magnesium, ammonium phosphate
-“Coffin-lid”
-Common in normal SA urine
-Plug of blocked male cats
-Cattle on high grain diets with low Ca:Phos ratio
-Occur with bacterial UTIs, alkaline urine, increase dietary MG.
Calcium carbonate
-Brown spheres with radial striations
-Common in LA urine
-LA with high calcium intake (especially horses)
-They can get quite large
Calcium oxalate dehydrate
-Octahedrals with Maltese cross (X connecting four corners).
-Hypercalcemia/hypercaliuria, increase dietary oxalates, acidic urine, may be present with ethylene glycol toxicosis.
Calcium oxalate monohydrate
-Picket fence, hemp seed, and barbells like.
-Ethylene glycol toxicosis, or predisposing factors.
Calcium phosphate
-Rare in SA
-Appear as plates or needles
-Conditions promoting hypercalciuria and hyperphosphaturia
-hyperthyroidism, hyperadrenocorticism, distal renal tubular necrosis.
Ammonium biurate
-Yellow-brown, thorny apples like
-May also appear as smooth sphere
-Rare in SA
-Except Dalmatian and English bulldog -impaired ability to convert uric acid into allantoin.
-Suggests hyperammonemia or increased uric acid
-Urolithiasis in cats frequent idiopathic
-With portal vascular anomalies, hepatic dysfunction
Xanthine
-Can not differentiate from ammonium biurate, need infrared spectroscopy or liquid chromatography
-May occur secondary to allopurinol treatment in dogs
-Obsreved in CKCS and Dashunds with inborn error of purine metabolism
-Observed in cats with defect in xanthine oxidase activity
Uric Acid
-Yellow to yellow-brown diamonds or rhomboidal plates
-Sometimes have concentric rings
-Rosettes may develop
-Ocassionally hexagonal
-Same significance as irate crystals
Cystine
-Colorless, flat, and hexagonal, may appear layered
- Uncommon in SA
-Never normal
-Genetic screen with PennGen
-Suggests inherited defect in cystine metabolism
-May lead to Uroliths
-Promoted by acidic urine
Amorphous
-German shepherd dogs prone to silicate uroliths
-Include phosphate, urate, xanthine, silicate components.
-Alkaline urine = phosphate
-Acidic urine = urate
Ruminants grazing on silica-rich soil prone to silica urolithiasis
B. Other Crystals
Bilirubin
-Golden, golden-brown needles
-Ocassionally in normal dogs with concentrated urine
-Sign of cholestasis disease (hepatic or post-hepatic hyperbilirubinuria)
-Less commonly associated with IVH
Sulfonamides
-Fuzzy, brown, needle-like crystals in sheaves or rosettes.
-Can look as serrated transparent ovals
-Occur occasionally with sulfonamide treatment
-Usually associated with sulfonamide overdose
-Confirm with lignin paper test: wet paper with two drops or urine, add one drop pf 10% HCL immediately yellow-orange color = confirmation
C. Casts
Hyaline Casts: semitransparent with blunt or tapered ends. Refractive index similar to urine.
-Unaltered Tamm-Horsfall mucoprotein.
-2 per low-power field normal
-Increase with proteinuria, pyrexia, strenuous exercise, diuretics, passive congestion.
- Cellular Casts: can be RBCs, WBCs, epithelial cells, etc. More frequently WBCs.
-Less common indicator of acute renal injury compared to granular (degenerate)
-Epithelial casts suggest acute tubular necrosis
-WBC suggest infrarenal inflammation, acute bacterial pyelonephritis, less common interstitial nephritis.
-RBCs infrarenal hemorrhage. - Granular Casts: appear finely to coarsely texture with particular matter.
>1 pet 10 hpf (high power field) is abnormal
-Most common with renal tubular pathology
-Indicative of acute renal disease
-Cellular casts degenerate into granular casts when renal flow is reduced (increased transit time)
-tubular cell lysis directly forms granular cats - Waxy Casts: transluscent to gray-yellow. Thicker and denser than hyaline casts. More refractive and easier to detect.
-Uncommon
-Usually with chronic kidney disease
-Typically form in periods of long-term reduced urine flow-oliguric/anuric renal disease
-Reflect the end-stage of granular cast degeneration
-Broad waxy casts of collecting duct origin are associated with severe renal disease. - Lipid Casts: Interpret as granular cats
-Casts with adhered fat droplets that are incorporated from damaged lipid-laden renal tubular cells (occurs in cats and diabetic dogs) - Hemoglobin Casts: Yellow to golden brown with granular texture
-Mostly associated with intravascular hemolysis
-Rarely occur with breakdown of RBCs casts from renal hemorrhage
Urine sediments: cells and organims
Cells
Transitonal epithelial cells: normal lining found in urine
-Increase with Catheterized samples, cystoliths, inflammation, neoplasia, chemical irritation from renal excreted drugs.
-When abnormal, stain a dried sediment smear and review and/ or submit to a pathologist.
-BRAF test
Squamous epithelial cells
-May be keratinized (externally from skin origin) or non-keratinized (distal urethra, prepuce, vagina)
-Increase with catheterized or void samples, squamous metaplasia of the canine prostate, inflammation occurring at the squamous sites.
-Rule out testicular tumors when large numbers are present in intact male dogs.
Leukocytes
-spherical; colorless, grainy appearing cytoplasms.
-Most often neutrophils, but differentiation is difficult
-Larger than RBCs, smaller than transitional cells.
-Increase with inflammation or contamination of the urinary tract, interpret with collection method in mind
-Increased numbers should trigger stained sediment review.
Organisms
-Urine is sterile in health
-Females are anatomically predisposed to UTIs
-Glucosuria promotes UTI
-Uroliths create a nidus for UTI formation
-Prolonged antimicrobial use promotes resistance
-Increase corticosteroids endogenous or exogenous may induce immunosuppression
Bateria
-Rods easier to observe on wet-prep than cocci
-Should trigger a review of stained sediment
-Differentiate contamination from infection
-Real if: inflammation is present and bacteria are phagocytized
-Absence of bacteria does not rule out a bacterial UTI
-Culture is always recommended for confirmation and antibiotic sensitivity testing.
Fungal
-Less common
-Usually opportunistic organisms in immunosuppressed patients
-Hyphae and yeast may be observed
-Candida spp. are most common
-Fungal culture with PCR is always recommended for confirmation and speciation
Other
-Rare: Prototheca spp., Capillaria/Pearsonema spp., Dioctopyma in dogs.
Renal function lecture 1
- Discuss laboratory tests commonly used to evaluate renal function
- Explain advantages and limitations of these tests
- Interpret results and identify abnormalities frequently associated with renal disease
- Differentiate glomerular from tubular disease
- Differentiate pre-renal, renal, and post-renal azotemia
- Differentiate acute from chronic renal failure
- List etiologies for acute or chronic renal failure by species
Review of Renal Function
What is needed to concentrate urine?
What percent loss of nephrons results in inability to concentrate urine?
-Fluid and solute regulation
-Conservation of plasma proteins
-Waste removal
-Acid-base balance
-Synthesis functions
Renal plasma flow = plasma flow to the glomerulus
GFR is directly proportional to RPF
Blood flow to the nephron
-Renal artery and segmental branches
-Afferent arteriole
-Efferent arteriole
-Vasa recta: vastly responsible for supplying O2 to the remaining nephron
-Venous return
-If segmental branch of the renal artery is occluded (embolism) the entire renal segment will eventually necroses.
-There is no regeneration of renal parenchyma, remaining cells must undergo hypertrophy to retain GFR
Glomerular filtration
-Freely pass: water, Na, K, Cl, HCO3, Urea, Creatinine, Glucose, small proteins (light chains), conjugated bilirubin
-Large stain in plasma: albumin, unconjugated bilirubin, immunoglobulins, lipoproteins, WBCs, RBCs, Platelets.
Kidneys can maintain H2O retention until ~66% of function is lost
< 33% function = polyuria
Proximal Tubule
-Most everything immediately resorbed
-Renal threshold for Glucose
Dogs: 180 mg/dl
Cats: 280 mg/dl (200 mg/dl if diabetic)
Horses: 160 mg/dl
Cattle: 140 mg/dl
Loop of Henle
-Fluid solute regulation
-Drops deep into the medullary gradient
-Descending loop: water resorption along with urea, Na, Cl, enters filtrate. Reaches highest osmolarity at the bottom
-Ascending limb: impermeable to water, lots of solute absorbed, reducing osmolality and adding to medullary gradient.
Antidiuretic hormone (vasopressin)
-Distal nephron site of important hormonal control
-Produced in the hypothalamus, stored in the pituitary
-Upregulates aquaporins - increase H2O reabsorption
Without it or if resistance to ADH = polyuria, diabetes insipidus
Aldosterone
- Salt conservation: actively exchanges Na, K, and H,
-Cl follows Na, water follows too (if ADH active)
-If academia or hypokalemia are present, a separate pump results in HCO3 formation, K absorption, and excretion of Cl and H.
What is needed to concentrate urine?
- A medullary gradient
- ADH
- Tubules responsive to ADH
What percent..?
66% = unable to concentrate urine
75% = Renal Azotemia
What does the kidney produce? Conserve? Excrete?
Produce
-Vitamin D: Major exception horses, they lack 1-alpha-hydroxylase. Instead of calcitriol horses make small amounts of 24,25,-DHCC (vitamin D3). GI absorption of dietary calcium in horses is based on the amount consumed rather than vitamin D activity.
-EPO (erythropoietin): mainly produced in response to hypoxia by renal peritubular interstitial cells. HIF-alpha is not degraded as it normally is when there is hypoxia, then it activates transcription of EPO. Rate of EPO transcription is inversely proportional to the O2 carrying capacity of blood. EPO acts as progenitor cells in bone marrow to stimulate increase of both red cell and platelet lineages. As erythrocytes increase the O2 carrying capacity increases and negative feedback for EPO occurs.
-Production lost/decrease with chronic renal disease
Conservation
-Na, Cl: initiating stimuli is dehydration, Na deficiency or hemorrhage.
-Ca: Mostly passively resorbed in the PCT. PTH promotes calcium resorption in the ascending limb of the loop of henle and the distal tubule. Renal calcium resorption promoted by calcitriol (minor effect). Exception horses, utilize the kidney as a major route of calcium excretion.
-Albumin, antithrombin II: generally decrease with renal disease. Healthy animals pass a small trace amount but typically reabsorbed by PCT. Trace amounts on canine urine dipstick is OK.
-Antithrombin II: Thrombotic disease- pulmonary thrombotic emboli, cerebral infarct, renal infarct, saddle thrombus (feline).
Excretion
-BUN
-Creatinine
-Phosphorus: Ruminants and equids exhibit extra renal excretion of phosphorus, primarily in saliva and the rumen of cattle. Carnivores take in more phosphorus therefore excrete more.
-Potassium
-Hydrogen
-Lipase
-Amylase
-Generally increase with renal disease
Azotemia Overview
What is needed to classify Azotemia?
-Accumulation of nitrogenous waste (urea nitrogen and creatinine)
-Reflects reduction in GFR; other decent GFR indicators = Phos, Mg,
-Primary indicator of renal disease in veterinary medicine
-Not synonymous with uremia
-Uremia: clinical manifestation of chronic renal failure. Anemia, cachexia, fibrous osteodystrophy, gastritis, hypertension, stomatitis.
Azotemia does not develop until renal functional capacity is reduced by 75%
Each doubling of elevated UN and creatinine reflects a 50% loss of remaining renal function
-Urine specific gravity needed: it varies with dehydration status
-Dogs: 1.030
-Cats: 1.035
-Large animals: 1.025
-Hypersthenuric: higher than adequately concentrated urine
-Hypoesthenuric: lower than adequately concentrated <1.008
-Isosthenuric range: 1.008-1.012 (66% function loss)
-Gray zone: 1.013-1.029
Pre-Renal Azotemia
-Dehydration artificially increases BUN & Creatinine - Azotemia detected
-Many reasons for pre-renal azotemia but NOT renal disease
Renal Azotemia
-Trashmen don’t pick up = Azotemia
Post Renal Azotemia
-Road is blocked, and trash backs up = Azotemia detected
The threshold for waste detection (azotemia) is static, regardless of which point along the axis the waste comes from; any combination of points may contribute
Pre-Renal Azotemia
-Mechanism: reduced renal blood flow
-Reduced RPF = reduced GFR
-Hopovolemia: dehydration very common
-Shock: systemic vasodilation
-Acute hemorrhage
-Loss of colloidal osmotic pressure (COP)
-Marked hypoalbuminemia
Response
-Increase release of ADH by hypothalamus
-Increase USG
-Increase H2O resorption in the distal nephron (sustained reduction of RPF will lead to renal hypoxia, acute renal injury, IV fluids needed).
-Juxtaglomerular apparatus detects decrease RPF and triggers RAS
-Aldosterone release from the adrenal glands
-Renal absorption of Na and Cl increased
-Renal plasma osmolality increased
-Stimulates thirst
Post-Renal Azotemia
-Disease distal to the kidney
-Urinary tract obstruction (very common in male cats and goats)
-Urolithiasis
-Mucoid plug
-Neoplasia
-Prostatic disease
-Rapture or leak of post-renal structures,
-Trauma such as foals increased abdominal pressure during parturition
-Hyperkalemia due to reabsorption from the abdomen
-Azomtemia may be moderate to marked (simulated anuria)
-USG is variable - use clinical signs to help differentiate (stranguria, etc)
-The resulting hyperkalemia can be fatal: Bradyarrhythmia
-Post obstruction renal azotemia can develop, trend renal profiles after resolution of inciting cause.
Renal disease Acute vs. Chronic
Acute
-Severity of azotemia does NOT differentiate
-Acute kidney injury (AKI)
-Abrupt renal dysfunction: may or may not be reversible
-Faster rate of azotemia increase than chronic renal failure
-Usually oliguric or anuric: little time for compensation by remaining nephrons
-Labs resemble post-renal azotemia
-USG can vary
-Usual etiologies: toxins, ischemia, infractions
Chronic renal disease (CKD) will lead to
-Renal Secondary hyperthyroidism (except equids): Decrease calcitriol =decrease Ca = increase PTH
-Mild to moderate non-regenerative anemia = decrease EPO
-Severe azotemia does not differentiate
-Slow, insidious onset: many nephrons have died off, remaining nephrons hypertrophy
-Slow rate of Azotemia increase
-Usually polyuric
-USG dilute: more solute is presented to the remaining nephrons - solute diuresis. Medullary tonicity may be affected by the disease. Damaged distal nephron cells less responsive to ADH
-Signs or uremic syndrome may develop: typically ANEMIA (all domestics) and HYPOCALCEMIA ( except horses).
-Usually a life time of gradual renal insults
CKD eventually becomes oliguric then anuric
-Episodes of azotemia spikes with acute reduction in urine production in chronic renal disease - hyperkalemia develops
- Renal insufficiency: GFR 20-50%
- Renal failure: GFR <20-25%
- End stage: GFR <5%
Disease in one part of the nephron will lead to disease in all other parts
-Glomerulus: glomerulonephritis, amyloidosis
-Tubules: nephrosis
-Interstitium: interstitial nephritis
-Renal pelvis: pyelonephritis
-Urine Protein:Creatinine: magnitude and significance of proteinuria
-Run only when there is proteinuria in the absence of an active sediment (presence of RBCs, WBCs, or bacteria in the urine)
-Ratio >0.5 abnormal
-Glomerular proteinuria (more severe) assumed with ratio>2.0 and definitions at >5.0
-Acute tubular necrosis: damage from ischemia or toxins. Ischemia usually transient due to severe dehydration. Endogenous toxins: hemoglobin, myoglobin. Haptoglobin neutralizes what it can, then pigmentary nephropathy develops. Reversible if treated early on
Early Biomarker of Decreased GFR
-Symmetrical dimethylarginine. IDEXX
Osmolal Gap and Anion Gap
Osmolal Gap
-Need special equipment
-The difference between measured osmolality and calculated osmolality
Osmolal gap = mOSMO - cOSMO
-Recall calculated osmolality takes into consideration Na, K, BUN, glucose.
-The osmolal gap increases when a non-ionic osmole is present
-Pseudohyponatremia from a markedly lipemic or hyperproteinemic sample measured with indirect potentiometry will also result in falsely increased osmolal gap.
-Normal osmolal gap is < 10mOsm/kg
-If pseudohyponatremia has been ruled out, a result > 10 mOsm/kg indicates presence of non-ionic osmole such as:
Mannitol
Ethylene glycol
Ethanol
Methanol
Contrast media (radiographs)
only detects non-ionic osmoles because changes in ionic compounds is always balanced, resulting in unchanged osmolality
Anion Gap
-The difference between measured cations and measured anions.
Anion gap = (Na+K) - (Cl + HCO3)
-When increased beyond the upper RI limit, there are more unmeasured anions that under physiological conditions. Occurs when accompanying decrease in HCO3. This represents a high anion gap metabolic acidosis
-Increases in proteins will mildly increase the anion gap; likewise decreases in proteins will midly decrease the anion gap.
-The main unmeasured include:
Ketones
Lactate
Uremic acids
Metabolites of ethylene glycol
Salicylic acid (aspirin).
-Decrease anion gap values are not clinically significant and usually reflect hypoproteinemia
I. Background Information
Introduction
-The overall acid-base status is evaluated by measuring pH
-pH is the negative log of [H+]. Thus pH scale relates inversely with [H+]. It takes large changes in hydrogen concentration to change the pH.
-Normal blood pH is physiologically 7.4-7.5
-Slight variations occur between species and diets.
-Blood pH <7.4 = acidemia
-Blood pH >7.5 = alkalemia
-Changes in pH may reflect changes in H+ production, excretion, and/or buffering
-H is removed from plasma by buffers
-HCO3 (H2CO3) is the main buffer, though other buffers contribute
PO4, NH3, Sulfates, Hemoglobin, Albumin.
- Acid/base primarily regulated by kidneys and lungs
-Kidneys: PO4 and NH3 for excretion. Dogs have been shown to increase production of NH3 during acidemia. HCO3 is filtered freely and efficiently conserved. Acidemia stimulates aldosterone to excrete H+ and intercalated cells respond to states of acidemia with HCO3 synthesis.
-Lungs: expiration of CO2 drives H+ buffering. This process consumes HCO3 as well, but there’s significantly more HCO3 available than H+ that needs to be buffered. Because CO2 expiration drives H+ buffering, then partial pressure of CO2 (PCO2) can be used to assess respiratory acid status.
-Henderson-Hasselbalch: as ventilation increases, more CO2 is expired, H decreases alongside PCO2. As ventilation decreases less CO2 is expired, H increases alongside PCO2.
-Acid-base status is only completely assessed when arterial blood samples in conjunction with serum biochemistry.
-Blood gas does not tell you about mixed acid-base disturbances.
-Serum alone will only give an idea on metabolic side
-With renal and tubular acidosis urinalysis is additionally needed.
-Venous samples acceptable but can’t assess oxygenation (decrease pH and increased POC2)
-Arterial blood samples should be collected in a heparinized syringe, no air in the syringe.
Tests and Terms
-pH provides overall acid-base status
-PaCO2/PCO2: partial pressure of CO2 (a= arterial); represents the respiratory acid, use to interpret respiratory acid-base status.
-TCO2/HCO3: main base of the extracellular fluid, usually given as TCO2 on blood gas; represents the metabolic base, use to interpret metabolic acid-base status.
-PaO2: partial pressure of O2; idea of oxygenation
-BE: base excess, redundant when TCO2/HCO3
Simple Acid-Base disturbances
-Have a single primary disturbance (metabolic or respiratory), usually with compensatory response by the alternate system
-A primary respiratory disturbance is met with a compensatory metabolic response and vice versa.
-Note: compensatory response is almost never enough to normalize pH, except if the respiratory insult is chronic and mild. **If the untreated pH is normal you should consider the possibility of two primary opposing disturbances.
-Respiratory compensation begins immediately. Metabolic within hours but takes days to reach a peak response, but generally more effective
-In simple acid-base disturbances the pH matches the system abnormality and represents the primary disturbance, the arrows are in same direction.
II. Metabolic Acid-Base Disturbances
Metabolic acidosis
-Decrease TCO2 or HCO3
-Primary metabolic acidosis if decrease pH matches an acidemia
-Respiratory compensation decrease PCO2, increased expiration = increased H+ buffering. Tachypnea expected.
Primary metabolic acidosis with compensatory respiratory alkalosis
Major metabolic acidosis
-Titrational metabolic acidosis: a.k.a HIGH ANION GAP metabolic acidosis. Indicates increase in unmeasured anions that are acidic species. Ketoacids, lactic acids, uremic acids, ethylene glycol metabolites, salicylic acid. KLUES.
Diagnosis hinges on increased anion gap Organic acids are less likely to cause H+ shifts (all listed except salicylic acid).
-Ex: diabetic cat with ketoacidosis = tritational metabolic acidosis.
-Secretional metabolic acidosis
a.k.a hyperchloremic metabolic acidosis and normal anion gap metabolic acidosis.
-Characterized by loss of HCO3. GI origin, diarrhea (calf scours), LA salivary loss, vomiting of intestinal contents (rare). Renal origin, renal tubular acidosis HCO3 loss in proximal tubular or lack of synthesis in the distal tubules; necessitates Cl retention.
**Diagnosis hinges on a disproportionately increased Cl and Na, recall corrected chloride.
Minor metabolic acidosis
-Dilution metabolic acidosis (FYI)
-A small acidic effect that results from dilution of plasma with free water gains or rapid IV fluid infusion. Negligible.
Metabolic Alkalosis
-Increased TCO2 or HCO3
-Increased pH when it matches an alkalemia
-Increased PCO2 decreased expiration = decreased H+ buffering. Bradypnea expected.
-Primary metabolic alkalosis with compensatory respiratory acidosis
Major metabolic alkalosis
-Hypochloremic metabolic alkalosis
Minor metabolic alkalosis (FYI)
-Contraction alkalosis: increased HCO3 due to loss of HCO3 poor fluid commonly with hypochloremic
-Renal loss of H+ loop or thiazine diuretics. Hypokalemia K resorption costs H+
-Intracellular shifting of H+ during hypokalemia.
Hypochloremic metabolic alkalosis
-Occurs due to loss or sequestration of HCL
-Companion animals typically due to vomiting or pyloric outflow obstruction
-Cattle: abomasal sequestration
-Horses: esophageal reflux, ileus
-May present with paradoxical aciduria: may occur with concurrent hypovolemia. Under RAAS influence Cl typically is absorbed along with Na, but with previous loss of HCl, Cl is temporarily sparse in the urine.
H+ and K are lost to maintain electroneutrality, thus the urine is acidic despite alkalemia
Respiratory Acidosis
-Increase PCO2 decreased expiration = decreased H+ buffering
-Primary respiratory acidosis when pH decreased
-Compensation: Increased TCO2 or HCO3
Primary respiratory acidosis with compensatory metabolic alkalosis.
-Hypoventilation: includes decreased respiratory rate, but also other factors - dead space, functional alveoli, etc.
-Diseases that impair alveolar gas exchange: infection, pneumothorax (spontenous in Huskies!), pulmonary fibrosis (WHWTs!), tracheal collapse, pleural effusion, neoplasia, diaphragmatic hernia.
-Respiratory muscles inhibition: tetanus, botulism, tick paralysis, severe hypokalemia, myasthenia gravis.
-Drugs, anesthetics, sedatives, narcotics
-Brain stem disease.
Respiratory Alkalosis
-Decrease PCO2, increased inspiration = increased H+ buffering
-Increase pH
-Compensation: decreased PCO2 or HCO3
-Note: with chronicity this compensation may normalize pH
-Primary respiratory alkalosis with metabolic compensatory metabolic acidosis.
-Occurs with hyperventilation: hypoxemia, altitude sickness, severe anemia.
-Heat stroke, septicemia, drugs (salicylates) and aminophylline.
-CNS disease
-Pain/anxiety
