Pathophysiology Exam 4, Summer 2015
spironolactone
• Unique K+ sparing diuretic • Achieves its effect by being an aldosterone antagonist, not acting directly like other K+ sparing diuretics
in the US, ____ is the leading cause of end stage renal disease (ESRD)
#1 = diabetes mellitus #2 = systemic HTN
layers of the kidney
(outer part) - capsule - cortex - medulla (inner part)
fracture site blood loss
(see picture)
Primary Gout
- A metabolic defect in uric acid metabolism: increased production, decreased excretion or both
symptoms of carcinoid crisis
- A potentially life-threatening complication of carcinoid syndrome - may occur spontaneously or may be provoked by stress, chemotherapy, or biopsy. Clinically, this manifests as: - intense flushing - diarrhea - abdominal pain cardiovascular signs: - tachycardia - hypertension - hypotension
RA pathophysiology
- Idiopathic inflammatory disease with systemic involvement - Women>men - Most common ages 30-50 - Autoimmune response - 90 percent of patients with RA have auto antibodies called rheumatoid factors detected Pathogenesis - Antigen-antibody complexes activate inflammatory cells in the synovial fluid - Inflammatory cytokines (TNF-α, IL-1) induce enzymatic breakdown of cartilage, bone converting synovium into a thick, abnormal granulation tissue (pannus) Pannus - mass of intraarticular degradation tissue- immobilizes the joint
RA management
- AVOID NECK FLEXION!!! - Could see cord compression or compression of vertebral arteries = DEATH - No cure, underlying disease process remains - NSAIDS Disease-modifying antirheumatic drugs - Retard disease progression - Toxic - close monitoring - Bone marrow suppression and cirrhosis Etanercept (Enbrel) Infliximab (Remicade) Adalimumab (Humira) - Corticosteroids Methotrexate Sulfasalazine - Atlantoaxial instability - Positioning! - 30-70% have TMJ involvement (synovitis in the TMJ along with swelling may lead to difficult airway) - Cricoarytenoid joint of the larynx (40% with severe RA) joint can become swollen, and possibly impair airflow (stridor, tenderness, pain on swallowing, dyspnea) - Laryngeal deviation, stiff neck Be aware of side effect from patient meds - NSAIDS: bleeding, plt dysfunction - Corticosteroids: HPA axis suppression (stress dose steroids), increased infection risk
gout pathophysiology
- Acute arthritis from uric acid (urate) crystals in joints - Disorder of purine metabolism - Uric acid (UA) is a waste product of purine metabolism - Serum uric acid levels rise to supersaturated levels, urate crystals form (↑ purine metabolism or ↓ renal excretion) - Crystals can deposit in synovial fluid, myocardium, aortic valves, renal, spinal regions - First metatarsal joint most common - Dx by the visualization of the uric crystals in joint fluid Implications: - Hydrate! Facilitate renal excretion of uric acid - Sodium Bicarbonate: helps to excrete uric acid - Possibly avoid LR (lactate can decrease uric acid excretion) - Check renal function - EKG abnormalities for myocardial involvement - Co-morbidites: HTN, DM, ischemic heart disease - Renal, GI and hepatic complications from meds
management of MG (myasthenia gravis)
- Anticholinesterase drugs: increase ACH at NMJ by inhibiting end plate acetylcholinesterase - Pyridostigmine, oral 3-6 hour duration 60 mg PO = 2mg IV - Thymectomy: for drug resistant MG or thymomas - Corticosteroids - reduces ACh receptor antibodies - Immunosuppressant drugs - Plasmapheresis: reduces circulating antibodies, can do before surgery Anesthetic Considerations: - High risk of aspiration (weak laryngeal muscles) - High chance of requiring vent support after surgery (informed consent) - Patients have an INCREASED sensitivity to non depolarizing muscle relaxation (vecuronium is 2x as potent) - Titrate to effect with a twitch monitor - Pyridostigmine inhibits true cholinesterase and plasma cholinesterase- could see an increase in SUX duration - Delayed hydrolysis/prolonged action of ester local anesthetics - Non depolarizing muscle relaxants- decrease initial dose by ½ or 2/3 and monitor twitches closely! - MG patients are resistant to SUX! Reason unknown! ED 95 dose is 2.6x higher than normal
generalized symptoms of SLE
- Antinuclear antibodies: ANA lab test, however cannot be solely used to dx - Butterfly rash: over cheeks and nose Hematologic manifestations: - Thrombocytopenia - Anemia - Leukopenia - Antiphospholipid syndrome (acquired Hypercoagulability) - Serositis/nephritis: - inflammation of the pleura, pericardium, peritoneum Nephrons- glomerulus MANIFESTATIONS: - Articular (involving joints) or systemic - Hands, wrists, elbows, knees - 90% of pt have arthritis symptoms - Avascular necrosis of femur head - Most common: arthritis and dermatitis - Tissue damage from vasculopathy from immune complexes
MG (myasthenia gravis) pathophysiology
- Autoimmune destruction/inactivation of post synaptic ACH receptors at the NMJ - 70-80% of functional ACH receptors are lost - Weakness with rapid exhaustion of voluntary skeletal muscles, and partial recovery with rest - Most vulnerable are skeletal muscles innervated by cranial nerves (ocular, pharyngeal, laryngeal): - Ptosis (droopy upper eyelid) - Diplopia (double vision) - Dysphasia (impaired communication ability) - Thymic hyperplasia in 70% of cases - Thymus gland plays a role in the pathogenesis of MG - Women in 3rd decade, men 6-7th decade - 50-125 in 1 million - Pregnancy exacerbates MG in 40% of patients - Presents with WEAKNESS of the extraocular muscles - ptosis and diplopia - May see other autoimmune diseases (RA, SLE) - Antibiotics, especially the aminoglycosides can aggravate weakness
SYSTEMIC SLE symptoms
- CV: pericarditis, pericardial effusion (30-50%), CHF, HTN - Pulm: pleural effusion, restrictive disease, atelectasis - CNS: vasculitis, depression, anxiety, psychosis, seizures, stroke - Renal: nephritis, proteinuria, hypoalbuminemia, hematuria, renal failure (40-50%) - Liver: elevated LFT's - Heme: embolism, anemia, thrombocytopenia - Skin: butterfly rash, discoid lesions, alopecia (70-80%) - Airway: cricoarytenoid arthritis, stridor, obstruction
organ effects of chronic kidney disease
- CV—all have CAD - Heme—anemic—5-8gms/dl is normal - GI—delayed emptying - Neuro—autonomic & peripheral neuropathy - Resp—pulmonary edema - Infection—frequent exposure to blood products - Endocrine—often have DM Electrolyte disturbances: - Na+ —water retention - Ca++ —prone to fractures - check K+ —fatal dysrhythmias
signs of fat embolism during GENERAL ANESTHESIA
- Decrease in arterial saturation - Low pa02 on blood gas - Decrease in ETCO2 - Tachycardia
glomerulus
- FILTER! - a tuft of capillaries surrounded by Bowman's capsule - comprised of capillaries derived from the afferent arteriole - supplied by an afferent arteriole - drained by an efferent arteriole - filters the plasma at a rate of 180 L/day - allows all but protein and polysaccharides to pass into the nephron
anesthetic management of Zollinger-Ellison syndrome
- Gastrin-secreting tumor in pancreas or duodenum Treatment: - PPI - H2-blockers Pre-Op Labs: - coags - LFT's Anesthetic Implications: - Lots of HCl— aspiration risk! - Treat appropriately: NG tube preop Be ready for: - low K+ - metabolic alkalosis - dry as a chip
overlapping characteristics of neprhitis and nephrotic syndromes:
- HTN - proteinuria - hematuria - Na+ retention - edema
pathophysiology of acute pancreatitis
- In 60-80% cases, causative factor is gallstones or ETOH abuse. - Other causes: AIDS, hyperparathyroidism, blunt-abdominal trauma, post-ERCP. - Pts present with excruciating belly pain that radiates to the BACK! - Sitting and leaning forward helps! - N/V frequent - feverish - shock occurs in almost 50%. - Increased amylase is hallmark lab! - Sick patients if it gets serious---death can ensue. - ICU management critical—fluids, fluids, fluids Anesthesia: - will rarely see acute pt's in OR, maybe in ERCP to remove obsx. Gallstone—which is a controversial treatment. - Treat as you would a trauma pt., i.e. full stomach precautions, etc.
RA clinical manifestations
- Insidious onset (acute onset in ~15% pts) Begins with general systemic manifestations of inflammation: - fever, fatigue, weakness, anorexia, weight loss, and generalized aching and stiffness weeks - months→ joints become painful, tender, stiff, swollen, warm, boggy (due to inflammation), ↓range of motion Metacarpophalangeal, proximal interphalangeal (PIP), wrists - later: weight-bearing joints Affects knees, feet, wrists, hands (usually in a symmetrical distribution) - 1 hr after rising (usually) Joint deformities: - Ulnar deviation - Boutonniere & swan neck deformities of finger joints
fat embolism risk factors
- Male gender - Hypovolemic shock - Intramedullary instrumentation - Bilateral knee replacements - Long bone fractures of the femur and tibia - Liposuction
osteoarthritis pathophysiology
- Most common joint disease - Weight bearing joints affected most (knees, hips, cervical and lumbar spine, feet) - Degenerative process that affects articular cartilage (different from RA as there is no systemic inflammatory response) - Morbid obesity has a role - Biomechanical stress, ligament stress Pathophysiology - Loss of articular cartilage due to mechanical stress and the activation of enzymes - destruction of cushioning structure - subchondral bone sclerosis, cysts, and microfractures - Overgrowth of bone around the area of articular damage can result in protrusions called osteophytes
SLE (Systemic Lupus Erythematosus) pathophysiology
- Multisystem chronic inflammatory disease Characterized by: - Autoantibodies - Nucleic acids, RBCs, phospholipids, lymphocytes, platelets - Antinuclear (anti DNA) antibody production MOST characteristic - Women > men - Infection, pregnancy, surgery may exacerbate - Antinuclear antibodies present in 95% of patients, nucleosomal DNA- complexes Diagnosis made with three out of four: - Antinuclear antibodies - Butterfly rash - Hematologic manifestations - Serositis/nephritis Drug-induced Lupus Erythematosus - Procainamide - Hydralazine - Isoniazid - D-Penicillamine - a-methyldopa
risk factors for non-alcoholic steatohepatitis (Nonalcoholic Fatty Liver Disease)
- Obesity (excess of intrahepatic triglycerides, impaired insulin activity, and additional release of inflammatory cytokines; these factors can lead to destruction of hepatocytes and disruption of hepatic physiology and architecture.) - Diabetes - Female - Pharmaceutical agents
chronic peptic esophagitis (AKA heartburn)
- Relatively common occurrence: - 1/3 of adults @ least once every 30 days. - Underlying problem seems to be in the resting tone of LES, reduced from 29 mmhg normally to ~13 mmhg. - Collagen vascular diseases may predispose to reflux.
symptoms of an acute porphyria attack
- Severe abdominal pain, vomiting, diarrhea • Autonomic system instability • Tachycardia, hypertension, less commonly hypotensive • Electrolyte disturbances • Skeletal muscle weakness that may progress to paresis or respiratory failure • Seizures may occur during an attack
drugs that may provoke mediator release and precipitate carcinoid crisis:
- Succinylcholine - mivacurium - atracurium - D-tubocurarine - Epinephrine - norepinephrine - dopamine - isoproterenol - thiopental
specific causes of coagulopathy in the patient with portal HTN
- The liver synthesizes most of the coagulation factors of the coagulation cascade. - hepatocytes produce a number of anticoagulant proteins (protein S, protein C, protein Z, antithrombin III) and the antifibrinolytic plasminogen activator inhibitor - The liver is also essential for clearance of activated coagulation factors from the circulation. - hepatic necrosis seen in cirrhosis - decreased production of clotting factors - decreased elimination of activated factors - malabsorption of vitamin K - platelet defects related to splenomegaly seen with portal HTN - increased PT/PTT/INR - decreased fibrinogen, factor counts, platelet counts
pathophysiology of fat embolism syndrome
- a fat particle that enters the circulatory system causing vascular occlusion - Fat embolism syndrome: when circulating fat emboli or macroglobules result in multisystem dysfunction - act as micro emboli in pulmonary system and cerebral vasculature Mechanical theory: - Fat droplets enter through torn veins - Platelets adhere to fat globules - Microvascular blockage of droplets can produce local ischemia and inflammation Biochemical theory: - Stress-related release of catecholamines after trauma mobilizes fat molecules from tissue - Free fatty acids - Trigger acute vasculitis (cerebral and pulm) - destroy pulmonary and cerebral endothelium, increase capillary permeability, and lead to pulmonary and cerebral edema - molecules group into fat droplets and eventually obstruct the circulation - Could explain non-traumatic fat embolism syndrome
nephron
- about 1 million per kidney - functional unit of the kidney - as plasma flows along the nephron, virtually all the fluid and solutes are reabsorbed by a number of active and passive transport systems anatomic parts: - Bowman's capsule - proximal tubule - loop of Henle - distal tubule - collecting duct
mannitol
- an osmotic diuretic that facilitates urine output by decreasing excess tissue and intravascular fluid - works in the proximal tubule of the nephron - it is a very LARGE molecule; given IV and pulls fluid with it (transient hypervolemia) as it moves through the bloodstream; eventually causes hypovolemia through osmostic diuresis (increased excretion of water) - increases renal blood flow through the local release of prostaglandins - with reduced GFR or renal failure, it may be retained in the extracellular fluid and WORSEN heart failure! a large 6 carbon sugar • Filtered but not reabsorbed in the proximal tubule - limits passive water reabsorption • Free radical scavenger • Interferes with renal concentrating ability • Can cause transient hypervolemia • Transient hyponatremia & decreased hemoglobin due to dilution • Transient increased K+ • Eventually can cause hypovolemia, hypokalemia (low K+), & hypernatremia (high Na+) if fluids and lytes not replaced
acetazolamide
- carbonic anhydrase inhibitor • Interferes with Na+ reabsorption and H+ secretion in proximal tubule • Weak diuretic • Used to: - correct metabolic alkalosis - alkalinize the urine - lower IOP (intraocular pressure) by decreasing aqueous humor - altitude sickness
child pugh scoring system
- developed specifically to predict surgical mortality in patients with cirrhosis. - It assigns points for five variables (total bilirubin level, serum albumin level, INR, ascites, and hepatic encephalopathy) that are combined into a single score to categorize patients into Child-Pugh class A, B, or C
Glycosuria signals ____
- diabetes mellitus or - the ability of the proximal tubule to reabsorb glucose has been temporarily exceeded by a heavy glucose load
drugs that may have prolonged action due to their complete or partial renal metabolism:
- digoxin - inotropes - amino gylcosides - vancomycin - cephalosporins - pcn - barbs - panc - vec - neostigmine - edrophonium - atropine - glyco - milrinone - hydralazine - sulfonamides
typical hemodynamic & physiologic presentation of the patient with liver disease
- diminished physiologic reserve with which to respond to surgical stress and, as a result, are at increased risk for bleeding, infection, hepatic decompensation, and death - hyperdynamic circulation is a prominent feature of hepatic insufficiency! - decreased SVR - increased CO - edema - Coagulopathy is very common - hypoglycemia, hyperglycemia or normal BG - Malnutrition and malabsorption - increased triglycerides - elevated ammonia - Vitamin deficiencies and hypoalbuminemia - ascites - risk of bleeding due to impaired synthesis of clotting factors & amino acid formation - Hyponatremia - hepatic encephalopathy - increased gastric volumes and delayed gastric emptying - increased risk of developing renal dysfunction - inflammatory response increased - susceptible to infections & metastasis - jaundice - hyperaldosteronism - hypokalemia - altered estrogen & androgen metabolism - deficiency of vitamin K with bleeding tendency - elevated vitamin K with necrosis & cancer - vitamin D deficiency with bone disorders - low B12 stores
Pathophysiology of fat embolism involves ___
- disruption of the adipose architecture of the bone marrow - defective fat metabolism in response to stress
anesthetic gases and their effects on the liver
- immune mediated hepatotoxicity • Rare auto‐immune disease following use of volatile anesthetics. • Most commonly seen with use of halothane. • Forms trifluoroacetyl metabolites that acetylate liver proteins thus changing conformation • Body sees these as foreign and attacks • Potential for metabolite formation with enflurane, isoflurane of desflurane. • Incidence of hepatitis is much lower with other agents due to lower rate of liver metabolism • Possible cross‐reactivity if exposed to halothane previously. • Sevoflurane is the only agent that does NOT have trifluroacetylated metabolites. - patients with liver disease typically have increased CO with low SVR; they will have an EXAGGERATED response to vasodilatory effects of anesthetic gases! Volatile Anesthetics • May produce mild, self‐limiting dysfunction post‐operatively • May be due to inadequate hepatocyte oxygenation due to decrease in SVR often seen with general anesthetics • α‐glutathione Ѕ‐transferase (α‐GST) is more sensitive marker for hepatocellular injury • Key is self‐limiting
anesthetic management of TURP (transurethral resection of the prostate) under GA
- involves resection via cystoscope with continuous irrigation of the bladder to aid in visualization and removal of blood and resected material - irrigating fluid may be absorbed rapidly via open venous sinuses in the prostate gland, which causes volume overload and hyponatremia - constellation of findings associated with absorption of bladder irrigation solution is called "TURP syndrome" - dilutional hyponatremia - TURP syndrome manifests principally with CV signs of fluid overload and neurologic signs/symptoms of hyponatremia - DRAW an AMMONIA level!! most common complications: - Bleeding requiring transfusions 2.5% - TURP syndrome (water intoxication) 2% - Dysrhythmias 1% - Extravasation of irrigation fluid 1%
things that can decrease BUN
- low protein intake - severe liver disease
results of portal systemic shunting
- may exacerbate hepatic encephalopathy by allowing ammonia and other metabolic byproducts to bypass hepatic clearance. Shunting of blood away from liver has multiple effects: • Positive: partially decompresses liver • Negative: Bypasses liver and its functions • Collaterals directly connect, or shunt portal blood flow to general circulation. - Shunting allows toxic substances from intestines to directly access central circulation. - Increased risk of infection - Critical pathology of encephalopathy - Cirrhosis is most common cause of portal hypertension
effect of acetaminophen toxicity on the liver
- metabolism of acetaminophen requires glutathione - depletion of glutathione leads to toxic intermediate - more than 4 grams can cause severe hepatic necrosis - levels greater than 300 mcg/mL at 4 hrs have toxicity in 100% of patients symptoms: - nausea/vomiting - fatigue - jaundice - RUQ pain - transaminases are high - hepatocellular pattern of liver injury treatment: - N Acetylcysteine (replenishes glutathione) - liver transplant Fulminate versus Sub‐Fulminate Fulminate • development of encephalopathy within 2‐8 weeks of onset of acute liver disease. • Coagulopathy is nearly always present • Poor prognosis without transplantation Sub‐fulminate • Symptoms occur between 8 weeks and 6 months of onset of liver disease (some say 2‐8 weeks of jaundice)
stress doses for corticosteroids
- minor surgery: pre-op corticosteroid dose + hydrocortisone 25 mg or equivalent - moderate surgery: pre-op corticosteroid dose + hydrocortisone 50-75 mg or equivalent - major surgery: pre-op corticosteroid dose + hydrocortisone 100-150 mg or equivalent every 8 hrs for 48-72 hrs
____ have active metabolites that may accumulate in the renal patient
- morphine - demerol
pathophysiology of hepatic encephalopathy
- most commonly caused by a build-up of ammonia when the liver is no longer able to remove toxic substances - GABA synthesis increases and patients are more irritable as an earlier sign of encephalopathy - personality changes, bad breath, constructional apraxia (unable to perform purposive actions), asterixis (tremor of hand when wrist is extended), coma - treatment: kayexalate to eliminate toxic enteric substances; limit protein consumption - portal HTN - shunting allows toxic substances from intestines to directly access central circulation. Increased risk of infection Critical pathology of encephalopathy
Intracellular contents released with rhabdomyolysis include ______
- myoglobin - phosphate - potassium
pathophysiology of rhabdomyolysis
- myoglobinuria - Breakdown of muscle fibers that leads to the release of muscle fiber contents (myoglobin) into the bloodstream Destroyed muscle cells release: - Myoglobin - protein pigment - potassium ions - phosphate ions - creatine kinase (CK) - Muscle may be ischemic, swollen, painful, edematous Causes: - crush or thermal injuries - malignant hyperthermia - muscular dystrophy - drugs (propofol, halothane, succinylcholine) - poor positioning for long cases - severe dehydration with sustained activity - prolonged immobilization (ICU patients) Complications: - Normally, blood proteins bind circulating myoglobin - In rhabdo the quantity of myoglobin exceeds the binding capacity renal damage with: - acidosis - increase in BUN and creatinine - high K+ (release of intracellular K) - low Ca++ (phosphate binds with Ca++) - Renal failure up to 30% with CK >5,000 IU/L
these are some of the 5 P's of compartment syndrome
- pain - paresthesia - pallor - pulselessness
things that can increase BUN
- protein intake - tissue breakdown - GI bleeding - dehydration
TURP syndrome is more likely to occur when:
- resection is prolonged (> 1 hr) - when irrigating fluid is suspended more than 40 cm above the operative field - when hypotonic irrigation fluid is used - when the pressuer in the bladder is allowed to increase above 15 cm H2O - large gland size - a lot of gland congestion
S/S of dilutional hyponatremia (TURP syndrome) include:
- restlessness - headache - irritability - confusion - blindness - coma - seizures - dysrhythmias In the awake pt, the CLASSIC TRIAD is: - increased systolic and diastolic BP with a widened pulse pressure - bradycardia - a change in mental status
Clinical signs of fat embolism in the OR include ___
- subconjunctival petechiae - PaO2 58 mmHg
rheumatoid arthritis can be distinguished from osteoarthritis by ____
- the affected joints - presence of rheumatoid factor
obesity hypoventilation syndrome
- the long-term consequence of OSA • Due to progressive desensitization of respiratory centers to nocturnal hypercarbia, the apnea becomes centrally-mediated, similar to CCHS (congenital central hypoventilation syndrome AKA Ondine's curse, although this is a misnomer)
acute kidney injury (AKI)
- the sudden inability of the kidneys to vary urine volume and content appropriately in response to homeostatic needs - most common cause: prolonged renal hypoperfusion • The kidneys are sensitive to damage due to their high metabolic rate and ability to concentrate toxic substances • Classified as pre-renal, renal and post- renal in origin - pre-renal is due to impaired renal perfusion - renal is due to actual tissue damage (hardest to overcome/correct) - post-renal is due to obstructive problems (kinked foley, calculi, prostatic hypertrophy) - classified as oliguric and non-oliguric in presentation - oliguric = - Urine output less than 0.5 ml/kg/hr • Pre-renal or renal in origin - non-oliguric = • Lower urine Na+ than oliguric failure • Lower complication rate • May be possible to convert oliguric to non-oliguric failure, possibly decreasing morbidity and mortality
bowman's capsule
- think HOLDING AREA!
carcinoid crisis
- tumors generally arise from enterochromaffin tissues and are found in GI tract but can occur in bronchi and lungs. - They secrete some nasty things including histamine, kallikreins, and other substances. - Rare to see effects of these substances because they are usually muted by the liver S/S of the disease process involve vasoactive processes, but only occur in a small percentage of patients: - facial/neck flushing - asthma - bronchospasm - hypotension - SVT - Acute events are related to manipulation of tumor or embolization of liver metastases S/S of carcinoid CRISIS: - A potentially life-threatening complication of carcinoid syndrome - may occur spontaneously or may be provoked by stress, chemotherapy, or biopsy. Clinically, this manifests as: - intense flushing - diarrhea - abdominal pain cardiovascular signs: - tachycardia - hypertension - hypotension
reduced LES pressure in chronic peptic esophagitis (AKA heartburn)
13 mmHg
the kidneys are the most highly perfused organs in the body, receiving ____ of the cardiac output
20-25 %
normal LES pressure
29 mmHg
compartment syndrome clinical findings
5 P's: - Pain - Pallor (Poor Capillary Refill) - Paresthesias - Pulselessness - Paralysis - Diagnosed by measuring compartment pressures 10-30 mmHg = Impending ischemia > 30mmHg OR 10-30 mmHg from diastolic blood pressure = Impending/established compartment syndrome (Need urgent fasciotomy)
you lose ____ of functional nephrons before you have symptoms of chronic renal failure; this is classified as DECREASED renal reserve
60%
Renal insufficiency
60-75% loss of functional nephrons
in acute kidney injury, an increase in serum Creatinine lags behind the decrease in GFR by _____
7-10 days • the serum Cr to GFR curve is exponential; therefore, a small initial increase in Cr reflects a marked decrease in GFR!
ESRD (end stage renal disease)
75-90% loss of functional nephrons
- inherited autosomal dominant disorders with variable expression. - The enzyme defects in porphyria are deficiencies rather than absolute deficits. - attacks occur more frequently in women - attacks most frequent during the third and fourth decades of life. - Acute attacks of porphyria are most commonly precipitated by events that decrease heme concentrations and thus increase the activity of ALA synthetase and stimulate the production of porphyrinogens. - acute attacks may also be precipitated by physiologic hormonal fluctuations such as those that accompany menstruation, fasting (such as before elective surgery), dehydration, stress (such as that associated with anesthesia and surgery), and infection
Acute porphyrias
Secondary Gout
Caused by: - Drugs: Chemotherapy, thiazide diuretics, ASA, Etoh - Conditions: Kidney failure, hemolytic anemia - Can lead to lysis of purine containing cells
rhabdomyolysis diagnostic criteria
Classic Triad: - Muscle pain - Weakness - Dark urine Lab-confirmed increases in: - serum muscle enzymes (Creatine kinase (CK) (CK is located on the inner mitochondrial membrane, on myofibrils, and in the muscle cytoplasm. Most common marker for muscle breakdown) - Normal CK levels between 5-35 units/L - rhabdo = 1000 units/L - AKF > 5000 units/L alanine aminotransferase (ALT) - primarily found in liver cells, some skeletal muscle aspartate aminotransferase (AST) - primarily found in skeletal muscle
What is the best reflection of GFR and renal function?
Creatinine Clearance (this requires a 24 hour urine collection so you can't order this on the day of surgery!)
deposition of circulating immune complexes containing antibody against ____ produces tissue damage in individuals with SLE
DNA
CV disorders associated with obesity
Hypertension: • Systemic: increased ECF resulting in hypervolemia and increased CO due to increased demand are 2 major causes. Hyperinsulinemia results in SNS activation and Na+ retention • Pulmonary: as a result of chronic arterial hypoxemia and increased pulmonary blood volume • Obesity is an independent risk factor for ischemic heart disease • CHF due to LV hypertrophy and non- compliance • Any change in CO is due to increase in HR rather than SV
drugs to AVOID if the patient has acute porphyria
IV anesthetics: - thiopental - thiamylal - methohexital - etomidate Analgesics: - ketorolac - phenacetin - pentazocine CV drugs: - nifedipine
fat embolism syndrome CLINICAL SIGNS
MAJOR: (TRIAD) 1. Neck, shoulders, chest, axillary or subconjuctival petechiae (50%) 2. Hypoxemia (pa02<60 mmHg) 3. CNS depression (cerebral edema) - Pulmonary edema leading to ARDS MINOR: - Tachycardia (>110 bpm) - Hyperthermia - Retinal fat emboli - Urinary fat globules - Decreased plt/hct (unexplained) - Fat globules in sputum - DIC
____ are a group of metabolic disorders each of which results from the deficiency of a specific enzyme in the heme synthetic pathway. - characterized by overproduction of porphyrins - heme is the most important porphyrin and is bound to proteins to form hemoproteins that include hemoglobin and cytochrome P-450 isoenzymes.
Porphyrias
fat embolism complications:
The chest X-ray may show evenly distributed, fleck-like pulmonary shadows (Snow Storm appearance)
Most common cause of acute liver failure in the US is ___
acetaminophen toxicity
recommended weight basis (TBW or LBW) for common anesthetic drugs for the obese patient
calculate TBW for: - Propofol: loading - Midazolam - Succinylcholine - Cisatracurium and atracurium: loading - Pancuronium* calculate LBW for: - Propofol: maintenance - Thiopental - Vecuronium - Cisatracurium and atracurium: maintenance - Rocuronium - Remifentanil - Fentanyl - Sufentanil
myasthenic crisis
cause: too little ACh - symptoms: severe muscle weakness - treatment: anticholinesterase drugs to increase ACh at the NMJ (pyridostigmine) - diagnosis: edrophonium test (Tensilon test) 1-2 mg IV Patient GETS BETTER! (diagnosis = myasthenia gravis)
cholinergic crisis
cause: too much ACh (overdose of anticholinesterase drug; excessive muscarinic stimulation) symptoms: muscarinic - muscle weakness - bradycardia - bronchoconstriction - salivation - miosis - abdominal cramps treatment: - atropine - pralidoxime (AChE reactivator) - diagnosis: edrophonium test (Tensilon test) 1-2 mg IV Patient GETS WEAKER + muscarinic symptoms = cholinergic crisis
____ is the most common cause of portal hypertension
cirrhosis
the most important and clinically useful measurement in rhabdomyolysis is ___
creatine kinase level
Proteinuria signals _____ damage
glomerulus (think: big holes in the filter!)
BUN is _____ than Cr in measuring renal function (due to the variability of urea production and tubular reabsorption of urea)
less accurate
Zenker's diverticulum
location: Upper esophagus - Pt may be predisposed to pulmonary aspiration, EVEN in the absence of recent food ingestion. - Surgical repair is indicated, so be prepared for ASPIRATION i.e. H2-blocker/Reglan/ Bicitra, RSI, "ramp" or R-Tburg
the primary defect in osteoarthritis is _____
loss of articular cartilage
what is the functional unit of the kidney?
nephron
Large particles like glucose increase urine ____ MORE than osmolality
specific gravity - specific gravity compares the WEIGHT of urine to that of distilled water - urine osmolality measures the NUMBER of particles per Kg of urine
RA complications
systemic complications: - Extrasynovial rheumatoid nodules: (20-30% of pts)over pressure points and in visceral organs - Cardiac: pericardial effusion - Pulmonary: pulmonary effusion, pulm nodules, decreased lung volume - Rheumatoid myositis: muscle weakness and atrophy - Atlantoaxial instability: excessive movement at the junction between the atlas (C1) and axis (C2) as a result of either a bony or ligamentous abnormality - Ligaments erode from rheumatoid involvement by burse around C2 - neck pain, headaches, arm and leg neuropathies, bowel/bladder dysfunction - Atlantoaxial instability: excessive movement at the junction between the atlas (C1) and axis (C2) as a result of either a bony or ligamentous abnormality
which diuretic DECREASES calcium excretion?
thiazide diuretics
myasthenic crisis is the result of ____
too little ACh
thiazide diuretics
• Act at distal tubule • Inhibits NaCl reabsorption • ↑ K+ excretion • ↓ Ca+ excretion (opposite effect of other diuretics) • Extreme diuresis when combined with a loop diuretic • ex. HCTZ
potassium sparing diuretics
• Acts at the late distal tubule and collecting duct • Inhibits Na+ reabsorption • Inhibits K+ secretion • Triamterene, amiloride
interstitial nephritis
• Allergic reaction, most commonly to sufonamides, allopurinol, dilantin and diuretics • Autoimmune diseases (lupus) or infiltrative diseases (sarcoid) • Causes: - ↓ urine concentrating ability - proteinuria - systemic HTN • Steroids beneficial, often reversible
laboratory abnormalities seen with liver dysfunction
• Aminotransferases Enzymes involved in hepatic gluconeogenesis ALT is specific to the liver. AST is less specific Usually look at AST/ALT ratio levels Alkaline Phosphatase Non specific to liver Isoenzyme are present throughout the body Increased AlK PHOS may indicate bile salt induced damage of hepatocytes Levels can remain elevated for several days INR: Increased INR associated with decreased survival Not a complete indicator Albumin Most abundant plasma protein Decreased albumin levels often seen in liver disease - Antigen and antibody testing is KEY to differentiating between types of viral hepatitis and/or autoimmune hepatitis - TEG (thromboelastography)
things that can alter serum Creatinine
• Cr is a function of muscle mass • Rhabdomyolysis or the ingestion of large amt of cooked meat can increase Cr production • Competition by cimetidine or trimethoprim for the same pump site as Cr can decrease Cr secretion • Erroneous measurement of Cr by some assays can occur if pt is in DKA or has had cefoxitin or flucytosine
Pickwickian Syndrome
• Daytime hypersomnolence • Arterial hypoxemia • Polycythemia • Hypercarbia • Respiratory acidosis • Pulmonary hypertension • RV failure
glomerulonephritis
• Deposition of antigen-antibody complexes in the glomerulus (clogs the glomerulus with inflammatory SLUDGE!) • Seen after strep infection or collagen disease Look for: - Hematuria - proteinuria - HTN - edema - ↑ Cr • RBC casts help in the differential dx (little dead bodies of the RBCs) • Prompt IMMUNOSUPPRESSIVE therapy is helpful Complications of acute glomerulonephritis include: - hypertensive encephalopathy - acute heart failure
blood loss in a TURP procedure
• Difficult to assess due to copious irrigation • Usually 3-5 cc/min during resection
TURP irrigation fluids and implications
• Distilled water- good visualization, but will cause hemolysis of absorbed. Only used for surgery where no venous sinus is opened • Sorbitol- metabolized to fructose and lactate. May also induce osmotic diuresis • Mannitol- can cause osmotic diuresis and hypervolemia • Glycine- inhibitory neurotransmitter which can cause transient blindness and hyperammonemia
hypothermia risk in a TURP procedure
• Due to cold (room temp) irrigation • Can contribute to dysrhythmias and bleeding
management of the patient with acute porphyria
• Enzyme-inducing drugs are the most important triggering factors for development of acute porphyrias - fasting, dehydration, stress, and infection are also important triggering events Signs/Symptoms of acute porphyria: • Severe abdominal pain, vomiting, diarrhea • Autonomic system instability • Tachycardia, hypertension, less commonly hypotensive • Electrolyte disturbances • Skeletal muscle weakness that may progress to paresis or respiratory failure • Seizures may occur during an attack Implications for Management: • If an acute attack is suspected, skeletal muscle strength and cranial nerve function must be assessed because of their association with impending respiratory failure and increased risk of pulmonary aspiration • Abdominal pain may mimic surgical pain • Minimize preoperative NPO • Administer D5NS • Avoid drugs as mentioned prior • Most patients safely anesthetized as long as appropriate precautions are taken Treatment of Crisis: • Remove triggering agent • B-blockers for HTN and tachycardia • Seizure should be treated with benzo's • Adequate hydration • Electrolyte disturbances should be treated aggresively • Hematin only specific therapy
Kidneys control make-up and volume of bodily fluids through:
• Filtration • Re-absorption • Secretion • Excretion
indications for mannitol
• Used for prophylaxis against ARF (acute renal failure) • Conversion of oliguric renal failure to non-oliguric renal failure • Decrease ICP (intracranial pressure) • Decrease IOP (intraocular pressure)
physiologic alterations associated with laparoscopic cholecystectomy:
• GETA to provide mech. ventilation and reduce risk of aspiration • OGT/NGT for decompression • Narcs ok---<3% spasm, in event of spasm: NTG, naloxone, glucagon • Insufflation associated with shoulder pain---combo of local infiltration, opioids, and NSAID best multimodal approach Effects of pneumoperitoneum: • Decreased venous return, ventilation, and CO • Increased SVR, PVR, MAP • Reduced GFR = decreased UOP during insufflation • Hypercapnia • Possibility of bradycardia 2/2 peritoneal stretch causing increased vagal tone
Treatment for hyperkalemia
• Glucose & insulin- redistributes K+ into cell • Hyperventilation- redistributes K+ (for every 10mmHg the PaCO2 decreases, the K will decrease 0.5 meq/L) • Bicarb- partial antagonism of effects & partial redistribution of K+ into cell • Calcium- antagonism (raises arrhythmogenic threshold) - Beta agonists (redistributes some K+) ex. albuterol • Dialysis & Kayexelate- removes K+ from the body
how do anesthetics affect kidney function?
• Inhalation anesthetics appear to impair renal autoregulation • All GA depress renal function to some degree, by small unknown direct effects and indirectly, by affecting the circulatory, sympathetic, nervous and endocrine systems • Neuraxial anesthetics alter renal function relative to the degree of sympathectomy and hypotension. • Ketamine may increase renal vascular resistance and decrease renal blood flow • Contrast dye can be nephrotoxic especially in the face of dehydration and/or co-existing diseases
polycystic kidney disease
• Inherited autosomal dominant trait CYSTS!! • Renal failure, usually in middle age • HTN and proteinuria common • ↓ urine concentrating ability early in disease • Cysts may also occur in liver, CNS • Dialysis or transplant usually necessary at some point
loop diuretics
• Inhibit Na+ & Cl- reabsorption in thick ascending loop of Henle • May increase RBF & redistribute RBF from cortex to medulla • ↑ K+ excretion (because of ↑distal tubule flow rate) • ↑ Ca+ excretion • ex. Furosemide, bumetanide
S/S of glycine absorption in a TURP procedure include:
• N/V • Fixed and dilated pupils • Weakness • Muscle incoordination • Ammonia toxicity causing encephalopathy and delayed awakening and visual disturbances • Visual disturbances and blindness
how to treat dilutional hyponatremia in TURP syndrome
• Na > 120 meq/L—treat with fluid restriction and Lasix along with supportive measures • Na < 120 meq/L—treat with 3% NaCl at a rate no greater than 100cc/hr and discontinue when Na reaches 120 meq/L
symptoms of hyponatremia during TURP and corresponding blood levels
• Na of 120 meq/L—confusion and restlessness/ threshold for severe complications • Na of 115 meq/L—somnolence, N/V, widening QRS and ST elevation • Na of 100 meq/L—seizures, coma, v- tach, v-fib
respiratory alterations associated with obesity
• Obstructive sleep apnea----->Obesity hypoventilation syndrome----->Pickwickian • restrictive lung disease • Dyspnea, orthopnea Pulmonary Derangements: • Restrictive ventilatory defect due weight on thoracic cage and abdomen, thereby impeding the motion of the diaphragm. • Reduced FRC, ERV, and TLC • 50% reduction in FRC of obese, anesthetized patients compared with 20% in nonobese • Small FRC leads to very rapid desaturation during laryngoscopy; therefore, preoxygenate as long as it takes to get iO2 >.9
risk factors for primary sclerosing cholangitis
• Often considered an autoimmune disorder • Progressive inflammation destruction and fibrosis of the bile duct. • The absence of bile leads to fat malabsorption. The bile accumulates in the duct, leading to liver cell damage and liver failure. risk factors: - Predominates in men < 40 yrs - Often pre-exists with inflammatory bowel disease No effective medication available. Interventions aimed at relieving cholestasis due to mechanical obstruction. Liver transplantation is only effective treatment
risk of bladder perforation in a TURP procedure
• Perforation of the resectoscope or bladder overdistension and rupture • Extraperitoneal is the most common, causing loss of return of irrigation fluid, diaphoresis, retropubic, lower abd, or shoulder pain • Large extraperitoneal or intra-abd rupture can manifest as a sudden increase or decrease in BP, and bradycardia related to vagal stimulation
risk factors for primary biliary cirrhosis
• Predominately in women between ages of 30 and 50 • Suggestive of auto‐immune mechanism. May also present with scleroderma or hypothyroidism. • Chronic cholestasis and progressive destruction of intrahepatic bile ducts. Eventual development of cirrhosis and portal hypertension Slow progression Treatment Urosodeoxycholic acid Cholestyramin Fat soluble vitamins and biphosphonate
functions of the kidney
• Regulate volume & composition of body fluids • Eliminate toxins • Provide hormones like renin, erythropoietin & the active form of vitamin D
Pre-op considerations for chronic renal failure patients
• Sensitive to CNS depressants - start slow • Active metabolites • Protein binding issues (because patients often have low albumin, so highly protein bound drugs have more active unbound drug circulating)
similarities & differences among the various viral hepatitis infections
• Share common features of inflammation of the liver. • Inflammatory process causes cellular death via necrosis or triggering apoptosis. • Common lab abnormality includes markedly increased aminotransferase levels. Etiology is via serological testing. • Various viruses act as triggers - The vast majority of cases of acute viral hepatitis in the United States are caused by one of four viruses: hepatitis A virus, hepatitis B virus, hepatitis C virus, or hepatitis D virus. - Hepatitis A virus is the most common cause of acute viral hepatitis (50%), - followed in incidence by hepatitis B virus (35%) - and hepatitis C virus (15%). - Hepatitis D virus occurs only in patients with hepatitis B and is present as a co-infection.
how does altered kidney function affect anesthetics?
• Some drugs may have prolonged action due to their complete or partial renal metabolism • Morphine and demerol have active metabolites that may accumulate in the renal patient • NSAIDs may cause acute interstitial nephritis and worsen renal failure • Currently used inhalation agents are minimally metabolized by the renal system
OSA (obstructive sleep apnea) associated with obesity
• airflow cessation > 10s and characterized by frequent episodes of apnea or hypopnea during sleep. • Diagnosed in sleep lab using polysomnography • Severity is measured by number of events per hr, >5 is considered sleep apnea syndrome • Manifestations: arterial hypoxemia and hypercarbia, systemic and pulmonary hypertension, RV failure, and polycythemia • Incidence: 2-4% of middle-age adults (male prevalence), 5% of obese (BMI > 30). • Obese patients develop OSA due to increased adipose and pharyngeal tissue. • Dilator muscles typically prevent airway collapse in asleep individuals, but the tone is decreased. In OSA patients, the redundant tissue coupled with decreased tone leads to apnea. The effects are potentiated when anesthesia is administered.
nephrotic syndrome
• s/s due to ↓ plasma oncotic pressure with resultant hypovolemia (peripheral EDEMA) • ↑ urinary protein excretion, Na retention, hyperlipoproteinemia • Risk of thromboembolic and infectious complications • Causes include: - diabetic nephropathy - glomerulonephritis associated with neoplasia - HIV - PIH (pregnancy induced HTN) • Due to relative hypovolemia, patients may develop ARF in response to diuretic therapy, especially elderly or pts on anti-inflammatories