First Aid Errata

First Aid Errata

May 18 Lecture

Love

acquired heart disease is something that happens after 6 months of age


Kawasaki's disease - immune response to gram positive infection (toxic shock) - complication = coronary aneurysms.  no specific lab test. Treatment = IV immunoglobin (IgG)

survivors grow up with abnormal coronary arteries (no adenosine response)

Kawashocki   - >8yo girls; refractory to IVIG; high incidence of aneurysms

Rheumatic heart disease - comes from previous strep infection.  polyarthritis (painful and swollen) antibody protein complexes in myocardium (Aschoff bodies) - mitral valve disease.  St. Vitus' dance - inflammation of basal ganglia (Sydenham's Chorea). (St. Vitus is the patron saint of dancers, young people and dogs.)

Pericarditis - lower preload = low stroke volume (diastolic failure).  JVD and hepatomegaly. -70-80% of cases idiopathic (probably viral); also post surgery.  treat with steroids. pericardiocentesis.  preload exaggerated with respiratory cycle and pulsus paradoxus present.


Myocarditis - viral etiology most common = entero (Coxsackie B) or adenovirus
patchy involvement - Echo shows dyskinesis.  MRI useful for Dx.  Biopsy may not show anything if normal area of heart is sampled.  Tx ACE ARB Beta blockers, digoxin (but proarrythmic), milrinone (a PDE 3 inhibitor; positive inotropic, vasodilating, also facilitates ventricle relaxation (positive lusitrope) by enhancing Ca++ ATPase reuptake by sarcoplasmic reticulum.

May 17 Lecture

good acid base tutorial website
http://fitsweb.uchc.edu/student/selectives/TimurGraham/Welcome.html


good congenital disease website
http://pediatriccardiology.uchicago.edu/mp/CHD/pcmedpro-CHD.htm

Goens

ASD

Qp/Qs normally =  Sat ao - Sat svc /  Sat pv - Sat pa  = 1 in normal hearts (cardiac output is the same to lungs and body)

How do you get this equation?  recall the Fick Principle

volume overload of right heart ((left to right shunt)

stretch of atria leads to afib

pulmonary htn.  Eisenmenger syndrome (irreversible pulmonary htn)

ASD silent but overload causes pulmonic systolic murmur.

split S2 (late P2)

VSD (paramembranous or muscular or supracristal) 

Q = P/R   direction of Q depends on resistance.  If pulmonary resistance is high there will be small shunt; i.e., after birth.  As PVR comes down, the shunt increases.

volume load on left atrium and ventricle.  RV handles extra flow as conduit chamber but left heart receives extra volume.

Qp/Qs > 1.5 = moderate symptomatic shunt

pulmonary HTN may progress to Eisenmengers

loud P2 narrow splitting S2

harsh high frequency murmur

small shunt at high altitude due to hypoxic vasonconstriction -

PDA

flow during systole and diastole   (pressure gradient present in both systole and diastole)

most likely to cause Pulmonary HTN

continuous murmur infraclavicular

roughens endothelium producing area where bacteria can stick (endocarditits)

Aortic stenosis

bicuspid valve - most common

pressure load - symptoms depend on how quickly load develops. LV hypertrophy = increased O2 demand;  coronary origins distal to stenosis and ostium is narrow = decreased coronary supply.

early systolic ejection click (like split S1) as aortic valve snaps open 

Coarctation of aorta

HTN in head and arm, not lower extremeties. risk of cerebral aneurysms, stroke

 Increased  O2 demand but supply is not decreased.

systolic murmur that spills into diastole, best heard over upper back.

radial femoral delay and radial pulse stronger than femoral

if with PDA, will see lower O2 sat in lower extremities. 

Combination Lesions

tetralogy of Fallot

shunt depends on resistance.   always some R to L, aorta sits on top of VSD.  pulmonary resistance = conus (dynamic obstruction) and valve (fixed) and distal resistance

pulmonary outflow murmur (stenosis)

Pulmonary stenosis with ASD

in systole, no effect on direction of flow through ASD

in diastole, tricuspid valve is open, so flow will decrease L to R

Coarctation with VSD

increase L to R shunt from higher resistance in aorta

Coarctation with VSD and ASD

increases Qp but reduces pressure in LA pts have less tachypnea (less pulmonary edema) versus pts with no VSD but no ASD

Aortic stenosis  and LV failure

diminished pulses in all 4 extremeties

inotropic drugs (drips)

opening DA with prostaglandins will increase systemic perfusion although O2 sat would be lower. 

VSD with bronchiolitis and Sat of 89%

treatment with oxygen will increase O2 sat but will also increase Qp/Qs from relieving hypoxic vasoconstriction.

but will produce congestive heart failure from increased pulmonary flow.

sending newborn with VSD from Albuquerque to sea level for surgery worsens L to R shunt by relieving pulmonary hypoxic vasoconstriction lowering RV pressure.

Hypoplastic left heart syndrome (single ventricle)

no LV and ASD

systemic flow occurs via PDA

Qp/Qs may be 3:1

pulses weaker in arm than leg (leg distal to PDA)

saturations = in arm and leg

life depends on PDA and ASD

brain development abnormal due to hypoxemia.

Aortic Stenosis with exercise

LV pressure increases with exercise.  myocardial O2 demand increases; risk of sudden death.

Love

cyanosis is apparent with 4 g deoxy Hb

normal vaginal birth squeezes out lung water.  Caesarean births may have tachypnea due to residual lung water.

transitional circulation

• PDA shunt reverses to R to L
• PFO closes when umbilical cord is clamped and sytemic resistance increases

• delayed by lung disease, altitude,

symptoms of cyanosis at SaO2 = 70%

adult = SNS activity - tachypnea, diaphoresis, 

newborn = no distress (same oxygen as in fetal life).  stable at PaO2 > 35 mm Hg.  fetal life has been termed "Everest in Utero"

comfortable tachypnea in adults - maintain minute ventilation with higher frequency

but not comfortable in newborns with higher work of breathing.

meconium aspiration plugs segments of lung.  

distinguish lung disease from heart disease by ABG on 100% O2

PaO2 goes from 30 to 50 with shunt (shunted blood never sees 100% O2)

PaO2 goes > 120 by treating V/Q mismatch

closure of ductus creates cyanosis in ductal dependent cyanotic heart defects:

• transposition of great arteries - switch of PA and Aorta - circulation in parallel, not series
•  need PFO to be stable 
• need PDA to be stable
• pulmonary valve atresis (no pulmonic valve)
• need PDA
• Tricuspid atresia
• need PFO and PDA (unless there is a VSD)

prostaglandin PGE used to keep PDA open (side effect = apnea) (countered by O2 treatment)

Total Mixing Lesions

• Truncus arteriosus - PA originates from aorta - total mixing in aorta
• total anomolous pulmonary venous return.  pulmonary venous return to RA.  Need PFO
• tricusid atresia.  all systemic return goes via PFO to LA
• hypoplastic left heart.  no LV so all pulmonary vernous return to RA through PFO.  total mixing in RA.

Tetralogy of Fallot

could be pink at birth, no R L shunt

management

increase systemic vascular resistance (legs to chest; iv fluids)

bring heart rate down (increase diastole)

Coarctation of Aorta

detect with 4 extremities blood pressure

VSD

no RV hypertrophy because R and L ventricles contract together.  LV hypertrophy due to increased diastolic filling due to L R shunt.  RV hypertrophy means Eisenmengers.

ASD

fixed splitting of S2 because RA volume stays high and doesn't vary with respiration.  diastolic filling through ASD.

May 11 Lecture

Shah

High compliance of bladder important in preventing post renal renal failure (high pressure in Bowman's capsule).

Micturition:  ANS modulates reflexes involved in micturition.  PNS facilitate voiding.  SNS facilitate storage. Somatics contract sphincter and can stop voiding.  Pontine micturition center is mainly inhibitory.  spinal cord damage = overactivity & incontinence.

Incontinence:  

1. Urge (failure to store)
2. Stress (failure to store; intrinsic sphincter deficiency; relaxation of pelvic floor muscles)
3. Overflow (failure to empty; BPH-urethral obstruction) 

Treatment of voiding disorders

• behavioral - 
• pharmacological 
• muscarinic antagonists - slow the bladder treats urge incontinence
• alpha blockers - inhibit prostate smooth muscle. treat BPH
• surgical - improve pelvic support structures; artificial sphincter

Ureters have pacemaker, propagation of urine to bladder

Kidney stones - phases of obstruction

1. increased ureteral pressure - increased renal blood flow
2. increased ureteral pressure - decreased renal blood flow
3. decreased ureteral pressure - decreased renal blood flow  (ischemia; renal damage)

risk factors
dehydration
high salt intake - increases calcium secretion (hypercalciuria)
acid urine - precipitates uric acid stones


kinds of stones

1. calcium oxalate - most common
2. uric acid
3. Struvite (Mg and ammonium phosphate) in recurrent UTI with urease splitting bacteria
4. Cysteine - autosomal recessive stone disease

Treatment

• alkalinize urine - uric acid stones
• hydration
• alpha blockers (expel stones)
• surgery

May 6 Lecture

Kanagy

Tx for hypertension
Ca channel blockers (e.g., verapamil) and K channel activators (e.g., minoxadil) dilate vascular smooth muscle.

circulating norepinephrine versus circulating epinephrine

 epi = increased cardiac output and vasodilation in muscle and liver (beta 2) Pressure does not change since increase in Q is balanced by decrease in R  (P = QR)

circulating norepi causes increased cardiac output (beta 1) and increased vascular resistance from vasoconstriction in most arteries and veins (alpha 1 and 2).  transient increase in heart rate is reduced via baroreceptor reflex.

May 3 Lectures

Roldan

in slide 5, the trivial to mild regurgitation % refers to percent of the population who show this, not the % regurgitation.

for slides no. 15 and 24 (compensated AS and AR), the increased contractility is due to beta adrenergic stimulation.


use Firefox not Internet Explorer to open.
a great PowerPoint by a friend and colleague on this topic is available at:
http://www.boom-outahere.com/cvpulmrenalConcepts/CV/Cardiac Valve Dysfunction.ppsx

April 29 Lecture

Bryce

vasculitis symptoms - fatigue, fever, weight loss

medium vessels:  Kawasaki's disease - vasculitis - usually of coronary arteries.  80% of patients < 4 years old.  viral trigger.  most common among children of Japanese and Korean descent.

small vessels: 

• Wegener granulomatosis - granulomas with necrosis and vasculitis
• Churg-Strauss syndrome - associated with asthma - allergic vasculitis

vein diseases

Spaulding

ABC rule - PQR                P = QR

hypotension = systolic BP < 90 mm Hg

shock = MAP < 60 mm Hg

1. cardiogenic
2. hypovolemic
3. vasodilation

Big picture    P = QR       decreased P = dec Q and/or dec R

• if decQ (cardiogenic, hypovolemic) then compensation is inc R (vasoconstriction)   (pale, cold skin)
• 
  
• if decR (e.g., septic, anaphylactic) then compensation is inc Q (tachycardia, SNS) (warm skin)

April 27 Lecture

Aurelius

Arteriosclerosis

• medial sclerosis
• arteriolarsclerosis - arterioles (<0.3mm diameter) - seen in malignant hypertension (thick intima)
• atherosclerosis - larger arteries (most often aorta) also coronary arteries, cerebral arteries, etc.
• deposition of atheromas common at bifurcation of arteries (favored by turbulent flow)
• microscopic appearance - all 3 layers are affected
• media - loss of smooth muscle, replaced with collagen and ground substance
• adventitia - fibrous thickening, inflammation
• intima - deposition of atheromatous plaque - receptors for LDL catch LDL in circulation.  Monocytes also enter intima (renamed macrophages once in intima).  macrophages eat LDL and become "foam cells".   fibrous cap formed.
• emboli - from broken plaques. 
• aneurysm
• dissecting - tear in intima = double barrelled blood vessel - seen in Marfan's
• arherosclerotic - > 5cm at risk for rupture
• coronary artery atherosclerosis - normally epicardial arteries involved (not intramusclular arteries)
• supply/demand properties (e.g., shovelling snow MIs)
• MI common with 70% narrowing of coronary artery (esp. if narrowing is acute)
• enlarged heart dangerous - one capillary serves one myocyte
• damage to muscle takes days to weeks to appear; scarring occurs after 2 months

April 26 Lecture

Ahmed

Wall tension = pressure x radius
                               thickness

hypertrophy is adaptive in decreasing wall tension thus oxygen demand

Oxygen Supply

• coronary blood flow = most important in determining oxygen supply
• Q = P / R        
• Q factors
• vasodilation (hypoxia most important)  hypoxia has direct effect on vascular smooth muscle and increases adenosine and NO.
• neural factors (alpha and beta)
• autoregulation
• cardiac cycle timing - most Q during diastole for left coronary artery - most during systole for venous   (RCA has more flow during systole)

      review of anatomy of coronary arteries and veins.  Coronary dominance is determined by origin of the PDA (posterior descending artery).  85% of population is right corornary dominant (PDA comes from right coronary artery)

exertional chest pain may indicate a supply problem (exertion increases oxygen        demand)

Oxygen Supply

• arterial oxygen content   = Hb x 1.36* x SaO2  + (PaO2 x 0.003)      (*ml O2 per g Hb  - 1 mol of O2 can bind with 1 mole of Hb = 22,400ml/mole/16,800 g/mol)
• extraction very high for heart so little reserve for increasing O2 delivery. 

Treatment

1. increase supply

  nitrates - vasodilate  ( The hemodynamic effects of nitrates include relaxation of conduit arteries, increased arterial compliance, increased venous capacitance, dilation of collateral vessels in the myocardium - http://www.ncbi.nlm.nih.gov/pubmed/1449098)

Valenzuela

increasing demand (O2 consumption) causes increased supply (lower resistance)

autoregulation - best in heart, brain, and kidneys

angina pectoris - precipitated by exertion (increased demand)

• classic (effort)
• vasospastic (associated with atheromas)
• unstable (at rest)

reducing risk factors (http://www.webmd.com/diet/ornish-diet-what-it-is)

Nitrates operate primarily by reducing PRELOAD - dilating veins >>> arteries  - don't increase O2 supply but decrease O2 demand.

side effects - nitrates oxidize ferrous iron to ferric (methemoglobin) - treated with methylene blue.  [metHb has high affinity for cyanide,  higher than cytochrome oxidase.]

Cyanide poisoning from food.  The cassava plant is now the world's third largest source of low cost carbohydrates especially for populations in the humid tropics, with Africa as its largest center of production. It originated in Brazil, and it is now brought to the world, especially to the African continent and all parts of Southeast Asia as well as many parts in the US. It is the principal source of nutrition for about 600 million people or even more around the world. The toxin in cassava is called "linamarin". It is chemically similar to sugar but with a CN ion attached. When eaten raw, the human digestive system will convert this to cyanide poison. Just a few pieces of cassava roots contain a fatal dose of cyanide.

Nitrates should not be used for right heart MI because reduced preload will worsen condition.

Nitrates plus beta or calcium channel blockers when combined have all beneficial effects for CAD.

• calcium channel blockers - vasodilate

Primary Cardiovascular Actions of Nitrodilators (http://www.cvpharmacology.com/vasodilator/nitro.htm)

Systemic vasculature

• vasodilation
      (venous dilation > arterial dilation)
• decreased venous pressure
• decreased arterial pressure (small effect)

Cardiac

• reduced preload and afterload
      (decreased wall stress)
• decreased oxygen demand

Coronary

• prevents/reverses vasospasm
• vasodilation (primarily epicardial vessels)
• improves subendocardial perfusion
• increased oxygen delivery

2. decrease demand

• beta blockers - decrease contractility, heart rate, BP
• calcium channel blockers -  decrease contractility, heart rate, BP

Colleran

vulnerable plaque have thin fibrous cap

HDL scavenges excess cholesterol and returns it to liver

HMG CoA reductase is rate limiting step for LDL cholesterol synthesis  (inhibited by statins)






Acid Base Practice Questions

 

 http://www.unmphysiology.org

April 22 Lecture

Danielson

acid base problems

case 1 metabolic acidosis.  HCO3 = 6 

Treatment of metabolic acidosis with THAM buffer
http://ajrccm.atsjournals.org/cgi/content/full/161/4/1149


interesting case from 1993 NEJM:
http://www.nejm.org/doi/full/10.1056/NEJM199302183280717

Note survival of pH 6.46!

A simple tool for deciding if small acid base disturbances are compendated or not is shown below.  For a respiratory disturbance if the PCO2 is changed by 12 (from 40 to 52) (from 40 to 28) and there is no compensation by kidneys, then the pH will be changed by 0.1 (from 7.4 to 7.3) (from 7.4 to 7.5).  For a purely metabolic disturbance, if the HCO3 is changed by 6 (from 24 to 18) (from 24 to 30) and there is no respiratory compensation then the pH will be changed by 0.1 (from 7.4 to 7.3) (from 7.4 to 7.5)

April 21 Lectures

Fisher

Rondon (case wrap up)

Beta agonists used to treat hyperkalemia can cause tremor.  This is enhanced physiological tremor (normal tremor in everyone is enhanced) via the action of beta agonists on muscle spindles

1 lactic acid = 1 proton + 1 lactate
1 proton + 1 HCO3 = reduction of   HCO3 = anion gap increases by 1
AG went up by 14 but bicarb only went down by 11.  conclusion = extra metabolic alkalosis. 

also extra respiratory acidosis (PCO2 > predicted from Winter's formula)

Mary Widow  "anemia of inflammation"  -  inflammation causes liver to produce Hepcidin which prevents mobiliztion of iron from iron stores.  Proton pump inhibitors (omeprazole) caused ATN.

April 20 Lectures

Danielson

acid secretion in alpha intercalated cells acidifies urine down to a minimum pH of about 4.1.  In the process a new HCO3 is produced.  these new HCO3s replace the ones lost during blood buffering of metabolic acids produced by tissues.  beta intercalated cells can secrete HCO3 into urine when there is metabolic alkalosis.

titratable acid is buffered by phosphate.  HPO4 - H2PO4. Titratable acid can be measured in the urine from the amount of sodium hydroxide needed to titrate the urine pH back to 7.4.  Can't increase much in acidosis because phosphate buffer is limited to the filtered load of phosphate and plasma phosphate is normally only 2.5 - 4.5 mg/dL. 
non-titratable acid is buffered by NH3 to NH4+ (trapped in tubule due to charge).  It is non-titratable because the high pK of ammonium means no H⁺ is removed from NH4⁺ during titration to a pH of 7.4..

glutamine synthesis is stimulated by acidosis.  iIn proximal tubule glutamine is metabolized to NH3 and 2 HCO3 (new bicarbonate).  Most important buffer for metabolic acidosis (can reach 300 mmol/day is severe acidosis).

Davenport Diagram

slope of buffer line is due to hemoglobin (major blood buffer).  steeper in polycythmia.  lower in anemia.  slope is zero for a bicarbonate solution (no buffer for changes in CO2; i.e., a buffer can't buffer itself)

bicarbonate buffer is for metabolic acidosis or alkalosis (steeper slope at higher PCO2)
hemoglobin buffer is for respiratory acidosis or alkalosis (steeper slope with higher Hb)

practice questions for acid base

Alas

Gul

Total GFR = gfr per nephron x total number of nephrons.  with nephron loss, gfr per nephron increases (increased Pc) so total GFR may be normal

1 in 9 of adults have chronic kidney disease

90% loss of GFR before uremic symptoms occur
Intact Nephron Hypothesis; remaining nephrons compensate for loss of nephrons
Trade Off Hypothesis; renal failure = increased ECF = stimulation of ANP = increased Na loss

Hb starts to decline when GFR < 40 (higher GFRs with diabetics).   treated with Epogen. 

ferretin < 100 ug/L = iron deficiency anemia

GFR is meaningful ONLY when patient is in steady state   not meaningful in acute kidney injury.

April 19 Lectures

Kanagy

Site 1 diuretics
Carbonic Anhydrase inhibitors - Na, Cl, HCO3 stay in lumen along with water.  side effect = metabolic acidosis (HCO3 lost in urine = not reabsorbed into blood)  Used as prophylaxis for acute mountain sickness (metabolic acidosis counters the respiratory alkalosis from hypoxia induced hyperventilation) and to reduce aquaeous humor formation in eye (glaucoma)

Site 1-5 osmotic diuretics; e.g., mannitol - volume expansion of ECF leads to decreased renin secretion = decreased aldosterone = Na loss H2O loss.

Site 2 - loop diuretics - most potent - prototype furosemide (lasix).  decreased Na delivery to macula densa (turns off tubuloglomerular feedback).  Inhibit Na, K, Cl tri-transporter.  hypokalemia causes metabolic alkalosis - and enhances digitalis toxicity.

Site 3 (distal tubule) - thiazides.  increased excretion of NaCl.  "low ceiling = limited volume loss".  inhibit Na-Cl symporter in DCT.   hypokalemia; hypercalcemia (reduced Ca secretion)
"Thiazides INCREASE calcium reabsorption. Two mechanisms have been proposed for this effect.  Thiazide blockade of the sodium-chloride-cotransporter in the distal tubule leads to volume depletion and elevates passive transcellular calcium and sodium reabsorption from the proximal tubule.  In addition, increased sodium delivery to the late distal tubule appears to increase calcium reabsorption in the late distal tubule. Together, these effects can lead to a significant reabsorption of filtered calcium.  This is opposite to the effects of the loop diuretics, such as furosemide which tend to cause calcium wasting. For that reason, the two classes of drugs have opposite effects on the formation of kidney stones with thiazides decreasing the frequency of stone formation and loop diuretics increasing the risk."

Site 4 (late distal tubule and collecting duct).  inhibit epithelian sodium channels (ENaC) = countering aldosterone; e.g. amiloride.  Potassium sparing diuretic.  Hyperkalemia causes metabolic acidosis.  blocking aldosterone also causes metabolic acidosis directly.  Aldosterone antagonists; e.g., spironolactone.    anti-androgenic effects.

Site 5 - vasopressin (V2) blockers -  increase urine volume.

also see:
http://www.cvpharmacology.com/diuretic/diuretics.htm


Danielson

pHa < 7.35 = acidemia   pHa > 7.45 = alkalemia

...osis versus ...emia.   acidosis is a condition due to respiratory or metabolic change.  initially causes acidemia but later pH may be compensated back to within normal range (called compensated acidosis).   Similar for alkalosis.

metabolic acidosis = low pH due to low HCO3.   caused by addition of acid or loss of HCO3 (e.g., diarrhea).     Winter's formula for expected PCO2 compensation.  expected PCO2 = 1.5 x HCO3.

"make it or take it"   make it = daily acid load from metabolism.  CO2 load =

metabolic alkalosis =  high pH due to high HCO3.  causes = gastric suction.  vomiting.  diuretics (contraction alkalosis). 

ROME   ( "respiratory opposite; metabolic equal)  describes pH change with PCO2 change (respiratory) and pH change with HCO3 change (metabolic).

Anion Gap (AG) = unmeasured anions  (mainly albumin).    Na+ - HCO3 - Cl = AG.
E-MUDPILES

Normal anion gap with metabolic acidosis (hyperchloremic metabolic acidosis). 
diarrhea; renal tubular acidsosis, CA inhibitors; HCl ingestion.

Osmolar Gap  = measured serum Osm - calculated serum Osm.  increases with increased serum solutes or ethanol, methanol.

http://www.anaesthesiamcq.com/AcidBaseBook/ab3_5.php

Main Use of Osmolar gap:
Screening test for detecting abnormal low MW solutes (esp ethanol, methanol & ethylene glycol

Fisher

proteinuria due to foot process effacement so more prevalent in nephrotic syndrome than in nephritic syndrome.

April 18 Lecture Dr. Rondon

Rondon

with complete block of renal blood flow (zero GFR) it takes several days for creatine in plasma to double.

Creatinine can increase in multiple ways independent of GFR; e.g., blocked secretion of Cr by tubule cells
BUN can also increase independent of kidney problems; e.g., GI bleed (BUN level increases in upper GI bleeding because patients become prerenal, secondary to blood loss)

AKI

• fluid overload

Fractional excretion of sodium (FeNa) = sodium clearance/creatinine clearance

= UNaV/PNa

AKI
1. pre-renal -

• decreased fractional excretion of sodium  (stimulation of aldosterone)  (unless patient is on diuretics)
• BUN/Cr > 20  hypovolemia stimulates ADH which increases urea reabsorption in medulla = increased BUN.
• fractional excretion of urea < 35% (low)  (reliable measure for patient on diuretics where FeNa is higher due to diuretic)
• decreased GFR due to low blood pressure/hypoperfusion.  compensated by autoregulation of GFR; i.e., afferent arteriole vasodilation mediated by prostaglandins (blocked by NSAIDS).  also compensated by efferent arteriole vasoconstriction mediated by AT 2 (blocked by ACE inhibitors and ARB).
• IV contrast dyes can vasoconstrict afferent arterioles

2. intrinisic renal

• tubular necrosis (ATN) - ischemic; e.g., following prolonged pre-renal hypoperfusion or toxic

endothelial damage - tubular injury = inflammation, obstruction of tubule

dilute urine, FeNa increased, FeUrea increased

oligouria - reduced urine volume:  normal glomeruli but damged tubules - mechanisms =

1. blockage of lumen by dead cells, blocked urine enters blood ("back leak");
2. increased tubuloglomerular feedback Na Cl to MD signals afferent arteriole vasoconstriction

indication for dialysis = no response to diuretics, also hyperK, metabolic acidosis refractory to treatment; uremia; progressive azotemia (BUN > 80-100 mg.dL)

• interstitial (AIN)

lymphocytes and eosinophils in interstital space

normal urine output (tubules not blocked)

• glomerular (Ann Richards)  (AGN)   acanthocytes (Mickey Mouse hat)

• vascular -  microvascular (TTP),  macrovascular (renal artery thrombosis)

3. post renal - obstruction of both ureters OR in bladders (e.g., BPH) or urethra

increased pressure in Bowman's capsule decreases GFR.  hydronephrosis = dilation of kidney

April 15 Lectures

Chang

sterile below vocal chords

surfactant in alveoli is bacteriostatic (plus macs, lysozymes)
particle size  > 5 um deposit in upper airways   1-2 um can make it to alveoli (most bacteria)
virulence counts - TB less virulent than Klebsiella

colonization

direct innoculation

• aspiration
• esophageal rupture (severe vomiting - Boerhaave's syndrome)
• dental abscess; pyelonephritis (tracking fascial planes)

anaerobic pneumonia = patient with teeth

lobar pneumonia  -  spreads via pores of Kohn (openings between adjacent alveoli)

calcified lung lesions = previous TB  - tend to be in upper lobes because (she meant to say) oxygen levels are HIGHER.  Multiplication of Mycobacterium tuberculosis is favored by a high oxygen tension (high V/Q in upper lungs results in higher PO2 and lower PCO2).

chronic fungal infections:

• blasto, southeast  (duck hunters)  (includes extrapulmonary diseases)
• histo, Mississippi valley
• cocci, southwest, southern AZ, central valley of CA  ("valley fever")

pneumonias

pleural effusion

• parapneumonic effusion (no organisms)
• empyema (with organisms)
• empyema necessitans (flourishing bacteria eats way out of pleura)

April 14 Lecture

Kanagy

plasma = 300 mOsm    maximum concentration = 4 fold = 1200 mOsm    maximum dilution = 10 fold = 30 mOsm

tip of loop of Henle in tissue with 1200 mOsm in humans.   longest loops in desert rats (never drink water - get all water from food metabolism).
"shortest loops in marine mammals";   not really - marine mammals can concentrate their urine by 8 fold (2400 mOsm) allowing them to drink sea water (2000 mOsm) and get some net water gain from sea water.  freshwater mammals; e.g., Beavers, do have shorter loops of Henle

ADH  osmoreceptors in hypothalamus  ADH secreted in posterior pituitary

ADH secretion also stimulated by decreased blood pressure.  carotid sinuses most important (not cardiac baroreceptors)

ADH=AVP    vasoconstriction via V1 receptor Gq via phospholipase C.    Antidiuresis via V2 receptor cAMP - PKA - phosphorylates aquaporins - inserts aquaporins in luminal membrane (modulated by PGE2 - fine tuning of water reabsorption),  also inserts urea channels adding urea to interstitial fluid. 

Free water clearance

total clearance = water clearance + solute clearance

urine volume = Cwater + Cosm

or Cwater = urine volume - Cosm

example for dehydrated person:  urine volume = 1 ml/min   Uosm =1000 mOsm  Posm = 333 mOsm

Cwater = 1 ml/min  -   (1000 x 1)/333 = 1 - 3 = - 2 ml/min

for overhydrated person: urine volume = 10 ml/min   Uosm = 30 mOsm   Posm = 300 mOsm

Cwater = 10 ml/min - (30 x 10)/300  = 10 - 1 = 9 ml/min

April 13 Lectures

Scariano

40-80 mg/day = normal protein in urine 
<300 mg.dL = microproteinuria        >300 mg/dL = macroproteinuria

"foot strike hemolysis" in long distance runners = urine findings

ketones = acetoacetate and hydroxybutyrate  (conjugate bases of their acids) (contribute to anion gap of metabolic acidosis)

specific gravity - normal range 1.003 - 1.035  (distilled water = 1.000)

pH  minimum pH of urine about 4.5  ([H] = 0.03 mEq/L)

oval fat bodies - hyperlipidemia associated with nephrosis.  low albumin levels stimulate hepatocytes to produce lipoproteins = hyperlipedemia.

red blood cells - dysmorphic erythrocytes = acanthocytes - acanthocyte is derived from the Greek word "acantha" meaning "thorn." imbalance in membrane lipids causes cells to stiffen, wrinkle, pucker, and form spicules.

Rohrscheib

60:40:20 rule   Intracellular volume is 2x extracellular.  therefore, K is major cation of the body.

Ins and Outs:   GI loss is normally 10% vs. renal at 90%. 
GI loss increases with diarrhea; K =30-40 mEq/L in diarrhea fluid.  can lose 5L or more (e.g., cholera) per day.


a good review of K and ECG.  ECG findings can be understood from high K effects on cardiac myocytes and nodal cells (decreased slope of phase 4 = bradycardia). 

Myocyte

solid line = normal; dashed line = hyperkalemia.  decreased slope of phase 0 causes slowed cell to cell conduction time (long PR interval; widening of QRS). Increased rate of repolarization (higher conductance of K channels) causes peaked T wave.

Practice question: Predict effect of Bartter and Gitelman syndromes on plasma Na and K.

April 12 Lectures

Danielson I

Clearance of creatine = GFR   
amount of creatinine excreted is constant (depending on body size, muscularity) - this means that U x [Cr]u is constant.   The amount of creatinine leaving plasma is V x [Cr]p.
The amount leaving plasma is always equal to the amount in urine, so V x [Cr]p = U x [Cr]u.  For creatinine, V = GFR because there is only filtration, no secretion or reabsorption.

Using normal values; GFR x [Cr]p = U x [Cr]u or 125 ml/min x 1 mg/dL = 1 ml/min x 125 mg/dL

Renal failure = decreased GFR.  this means that plasma creatinine will be increased until new steady state is reached and urinary excretion is stable.

examples          GFR x [Cr]p = U x [Cr]u     62.5ml/min  x 2 mg/dL = 1 ml/min x 125 mg/dL
                                                                       41.2ml/min  x 3 mg/dL =  1 ml/min x 125 mg/dL
                                                                       50 ml/min x 5 mg/dL =  1 ml/min x 125 mg/dL

Danielson II

Proximal tubule

• early and late - filtered HCO3 is reabsorbed (Carbonic anhydrase essential for this)
• early - tight junctions - water not permeable; lots of cotransport of solutes
• late - organic acids sereted (antiporter with chloride); water reabsorbed via osmosis into blood  (volume expansion dilutes oncotic pressure in peritubular caps causing decreased water reabsorption - volume contraction (dehydration) leads to higher oncotic pressure and more water reabsorption. volume contraction can cause an alkalosis due to the stimulation of higher Angiotensin II (AT2)levels.  Increased AT2 stimulates Na-H antiporter leading to higher HCO3 levels in blood.

Contraction Alkalosis - also occurs passively with volume changes; e.g., due to diuretics.
http://fitsweb.uchc.edu/student/selectives/TimurGraham/Contraction_Alkalosis.html


Loop of Henle

• descending - permeable to water, salt, and urea
• thin ascending - salt reabsorption, no water
• thick ascending - not permeable to water - active transport of NaCl, K out of lumen into blood, dilutes lumen to hypotonic

distal tubule sourrounded by afferent and efferent arterioles; JGA fine tunes final salt excretion - aldosterone, ADH

• early - macula densa respond to JGA signals; reabsorption of NaCl, hypotonic fluid in DT
• late - principal cells and intercalated cells; NaCl, K reabsorption; water reabsorption (via aquaporin channels - regulated by ADH)
• collecting duct - aldosterone, ADH

Renin secretion regulated by blood pressure (also potassium, sympathetic NS)

Aldosterone receptor is transcription regulator.  upregulates pumps and transporters of principal cells. 

Practice question:  Conn's syndrome is a disease of the adrenal glands involving excess production of aldosterone (primary hyperaldosteronism).  Predict the effect of this condition of urine and plasma Na, K, HCO3, and pH.

Other practice questions


Barry

kidneys 0.5% body weight receive 25% of cardiac output = 1700 L per day = blood flow through kidneys       -  out of this the kidneys produce about 1 L of urine.

many diseases of glomerulus are immune mediated.  specific cause usually not known.
damage from in situ antigens (e.g., on podocytes) or by circulating antigen-antibody complexes (e.g., Lupus)

nephrotic syndrome - immune but not-inflammatory.  >3.5 g protein/day; hypoalbuminemia; hyperlipidemia (increased production by liver).  Enhanced hepatic synthesis of lipoprotein lipids may be stimulated by a decreased plasma albumin concentration or oncotic pressure (N Engl J Med 1985; 312:1544–8.)

urine - oval fat bodies.  Edema due to decreased osmotic pressure PLUS salt and water retention.

Minimal Change Disease  - damaged podocytes not seen with light microscopy - no immune deposits by immunoflorescence but immune dysfunction that damages podocytes

April 11 Lecture

Scariano

filtration fraction = GFR/RPF   glomerular filtration rate/renal plasma flow = 20%  (i.e., 80% of plasma is not filtered) prevents hyperviscosity of blood in efferent arterioles and peritubular caps.

filtration barrier to negatively charged molecules and to molecules > 70,000 kDa (albumin is 65,000 kDa but is negatively charged - 200 neg. charges per molecule)

GFR = 125 ml/min = 180 L/day  (Urine production = 1.8 L/day;  99% reabsorption)

Angiotensin II constricts efferent arteriole more than afferent arteriole.

How is GFR measured?  There is one way into the kidney (blood) and two ways out (blood or urine).  By using substances that are filtered from blood BUT not reabsorbed and not secreted into urine.  Clearance of substance X from plasma:  GFR [X]pv = Vu[X]u    In English, the amount of X leaving plasma = the amount of X in urine.  Amount = volume x concentration.    for plasma, volume = GFR and concentration = [X]p
for urine, volume = Vurine and concentration = [X]u.

amount leaving plasma = amount in urine = GFR [X]p = Vu[X]u   or GFR = Vu[X]u/[X]p  
note that the graph of [X]p = f(GFR) = y=1/X  = hyperbola.

Example of GFR calculation using lab data:
[Cr]u = 75 mg/dL  [Cr]p = 2.5 mg/dL     Vu = 1440 ml/day or 1/ml/min.



GFR = 75 x 1/2.5 = 30 ml/min

April 8 Lectures

Danielson

kidneys regulate concentration of substances in blood and urine.  Concentration = amount/volume.  Therefore, concentration can change in two ways - changing amount or changing volume

use this to measure volume:  volume = amount/concentration; e.g., 8g/8g/L = 1 L 


Osmolarity - the most important osmolytes (particles that contribute to plasma osmolarity) are sodium, glucose, and BUN.  Sodium dominates because it is the major osmolyte in extracellular fluid.  [Na] x 2 = plasma osmolarity estimate.  Normal = 290 mOsm/L


How is osmolarity regulated?  Osmoreceptors in the hypothalamus detect osmolarity and regulate secretion of ADH.


sea water has osmolarity about 8 times higher than plasma (about 2000 mOsm/L)


practice questions using volume diagrams: 

http://www.boom-outahere.com/boardreview/generalcell.html 



Naik

Important note: afferent and efferent arterioles are sites of resistance and that are in series; i.e., the total resistance is the sum of the two.  Rt = Ra +Re.  Need to Know how changes in Raff and Reff affect capillary P (GFR) and renal plasma flow (RPF).
Good summary figure from First Aid:

JGA line afferent arteriole. secrete renin and serve as baroreceptors.
glomerular caps = high pressure, high surface area, leaky (fenestrated) = high volume of filtration

peritubular caps = low pressure, higher oncotic pressure = high volume of reabsorption.  vasa recta caps maintain osmotic gradient.


myogenic reflex is primarily occurring in afferent arterioles.


macula densa cells in distal convoluted tubule sense salt and water delivery to DCT
feedback control.  inc. GFR = inc. Na delivery = release of adenosine, etc. = constriction of afferent arteriole = dec GFR.


JGA cells, increase stretch = depolarization = inc. Ca = DECREASE in renin release (opposite to neurons)


ANP dilates afferent and constricts efferent arterioles = double increase in GFR; decreases Na reabsorption in collecting duct
BNP from ventricle has longer half life than ANP = more useful as clinical marker.


Prostaglandins (PGI2, PGE2) don't alter renal blood flow under normal conditions but may buffer vasoconstriction effects; e.g., fight or flight sympathetic activation vasoconstricts both afferent and efferent but this is reversed by prostaglandins released by kidney.  also important in settings of volume depletion.  dangerous to use NSAIDS if volume depletion will occur.

 

April 7 Lecture

atelectasis pulls trachea toward collapsed lung
pleural effusion does not

transudate = pressure or oncotic imbalance - sytemic processes - usually bilateral

• increased venous pressure = increased capillary pressure = leading cause of pleural effusion in USA (500,000 per year)
• decreased plasma oncotic pressure = decreased albumin
• leakage of ascites through diaphragm

exudate = inflammation (increased permeability)

• inflammation of lung
• inflammation of pleural space

• parapneumonic effusion - Pneumococcus most common organism.  infected effusion = empyema
• pulmonary edema - exudative effusion near PE, blood tinged
•  

 pleural fibrosis - causes restrictive lung disease

April 6 Lecture

Danielson

pH 7.0 is neutral (i.e., pH = pOH) at  room temperature (20 C).

pH 7.4 is neutral at body temperature (37 C)

pH is determined by ratio of HCO3 / PCO2 or pH is determined by kidneys/lungs

pH = 6.1 + 1.3 = 7.4   1.3 = log 20    20 = [HCO3]/(PCO2 x 0.03) = 24/(40 x 0.03) = 24/1.2 =20 

If ratio is 20, pH will be normal.   COPD PaCO2 may be twice normal = 80 mm Hg.  Renal compensation will increase [HCO3} over time to twice normal = 48 mM.   Ratio will be 48/(80 x 0.03) = 48/2.4 = 20.

acid base practice questions
https://spreadsheets.google.com/viewform?formkey=dFV2U2lDbTJxZGFGLWtva3M4Sng1b2c6MQ

April 5 Lectures

Klepper

tension pneumothorax - air continues to enter thorax - through tear in lung  (tear forms a 1-way valve.

Boivin

pulmonary hypertension (PHTN)  = mean pulmonary artery pressure > 25 mm Hg (mean = 2/3 diastolic + 1/3 systolic)

direct sign of  PHTN = palpable P2

echo measures velocity of tricuspid regurgitation "jet" indirect measure of pressure in right ventricle.  also measures RV volume

Swan Ganz = gold standard

etiology PHTN       P=QR  

   increased Q  increased R

pneumonectomy - all Q goes through remaining lung but P does not increase since R decreases.  P = 2Q x 0.5R

Pulmonary embolism

S1Q3T3  (inverted T wave lead III)

Paul

pulmonary edema - 

hemodynamic

protein loss; e.g., GI diseases with diarrhea

microvascular damage

undetermined cause; e.g., high altitude; neurogenic (head trauma)

hemosideren laden macrophages in chronic pulmonary edema (stress fracture of capillaries leaks RBCs into interstitium.

causes of sudden death

central pontine hemorrhage

v fib

saddle pulmonary embolism (obstructs both right and left PA)

primary (idiopathic) pulmonary hypertension = death sentence  - due to inactivating mutations of BMPR2

secondary PHTN     inc P = inc Q or inc R  e.g., VSD, MS, thromboemboli,

Crookston

thrombin cleaves fibrinogen into fibrin.  thrombin also activates platelets.

fibrin monomers polymerize into clot.

hemophilia A,B, C

http://www.frca.co.uk/article.aspx?articleid=100096

Fibrinolytic pathway - activates plasminogen

natural anti-coagulants  and therapeutic anticoagulants (thrombin inhibitors; heparin which potentiates antithrombin).  low molecular weight inhibits factor X.

Warfarin (coumadin) in vitamin K antagonist.  (active ingredient of D-con rat poison)

INR measures extrinsic pathway