Muscle Types: Skeletal vs Cardiac vs Smooth

G protein coupled receptors - highest yield for cell, cv, pulm, renal, endo, Step1

In smooth and cardiac muscle. Not skeletal.

Skeletal Muscle - excitation contraction

                                                   

Excitation-contraction coupling of skeletal muscle. A muscle fiber is excited via the nerve by an endplate potential and generates an action potential, which spreads out along the surface membrane and the transverse tubular
system into the deeper parts of the muscle fiber. The dihydropyridine (DHP)
receptor senses the membrane depolarization, alters its conformation,
and activates the ryanodine receptor, which releases Ca2+ from the SR, a Ca2+ store. Ca2+ binds to troponin and activates the so-called contractile machinery.

Follow the JCI on:     
Copyright © 2016 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

http://www.jci.org/articles/view/25525/figure/1

Mechanism of action of succinyl choline:

phase 1 block

• Binding of suxamethonium to the nicotinic acetylcholine receptor results in opening of the receptor's nicotinic sodium channel; sodium moves into the cell, a disorganised depolarisation of the motor end plate occurs and calcium is released from the sarcoplasmic reticulum. This results in fasciculation.
• In the normal muscle, following depolarisation, acetylcholine is rapidly hydrolysed by acetylcholinesterase and the muscle cell is able to 'reset' ready for the next signal.
• Suxamethonium has a longer duration of effect than acetylcholine and is not hydrolysed by acetylcholinesterase. It does not allow the muscle cell to 'reset' and keeps the 'new' resting membrane potential below threshold. When acetylcholine binds to an already depolarised receptor it cannot cause further depolarisation.
• Calcium is removed from the muscle cell cytosol independent of repolarisation (depolarization signalling and muscle contraction are independent processes). As the calcium is taken up by the sarcoplasmic reticulum, the muscle relaxes. This explains muscle flaccidity rather than tetany following fasciculation.

Cardiac Muscle- signal transduction

http://www.cvphysiology.com/Blood%20Pressure/BP011a.htm

Smooth Muscle - signal transduction

http://www.cvphysiology.com/Blood%20Pressure/BP011b.htm

                           
               
                 

Why doesn't the heart cramp? - one reason is the long absolute refractory period of heart muscle cells compared with skeletal muscle cells.  Second impulse can't cause contraction if it occurs during absolute refractory period.

Your undergrad major is not important for medical school

If you weren't a biology major, that is not going to hurt you.  In fact, it may help you

Medical Students - Reason to Study Hard

Physiology of Running at High Altitude

https://secure.ultrarunning.com/archive/view-page.php?issue=91&page=28#top-nav

Practice test questions - pulmonary

1. A healthy 65-year-old man with a tidal volume (TV) of 0.45 L has a breathing frequency of 16 breaths/min. His arterial PCO2 is 41 mm Hg, and the PCO2 of his expired air is 35 mm Hg. What is his alveolar ventilation?

(A) 0.066 L/min
(B) 0.38 L/min
(C) 5.0 L/min
(D) 6.14 L/min
(E) 8.25 L/min

Hummingbird Physiology

Hummingbird Physiology

(just for fun)

body mass: 3-4 g

heart size: 2.5% of body mass (vs. 0.5% humans)

heart rate: 250 to 1260

respiratory rate: 250 (resting)

pectoral muscles: 25% of body mass (vs. 5% humans)

wing beats: 70 to 200 per second

body temperature: 40 to 18 C (torpor)

GFR: 2.5 (evening) 0 (night)

Suarez, R. K. (1992). "Hummingbird flight: Sustaining the highest mass-specific metabolic rates among vertebrates".Experientia 48 (6): 565–70.

http://jeb.biologists.org/content/207/25/4383.figures-only

High Yield Physiology, aka "Pearls"

A collection of medical physiology topics that are considered high yield; i.e., need to know for USMLE Step 1

High Yield Physiology, aka "Pearls"

Heart Disease in Women

Heart disease is the No. 1 killer of American women, affecting more women than men and causing more deaths than all forms of cancer combined.  Here are some other facts: 

- Ninety percent of women have one or more risk factors for developing heart disease

- The symptoms of heart disease can be different in women and men, and are often misunderstood

- While 1 in 31 American women dies from breast cancer each year, 1 in 3 dies of heart disease

- Hispanic women are likely to develop heart disease 10 years earlier than Caucasian women

- Cardiovascular disease is the leading cause of death for African American women

Tachycardia - treatment with adenosine

• Adenosine slows conduction time through the A-V node, can interrupt the reentry pathways through the AV node, and can restore normal sinus rhythm in patients with paroxysmal supraventricular tachycardia (PSVT), including PSVT associated with Wolff- Parkinson-White Syndrome. Intravenously administered adenosine is rapidly cleared from the circulation via cellular uptake, primarily by erythrocytes and vascular endothelial cells. Adenosine has a half- life of less than 10 seconds in whole blood.

ADMINISTRATION ROUTES: IV

ALTERNATIVE NAMES: Adenocor

ICU INDICATIONS:

1. Conversion to sinus rhythm of paroxysmal supraventricular tachycardia (PSVT), including that associated with accessory bypass tracts (Wolff-Parkinson-White Syndrome).

PRESENTATION AND ADMINISTRATION:

• IV: Adenosine comes in a vial containing 6mg in 2mls solution
• Compatible with the following IV fluids: Normal Saline Store at room temperature
• DO NOT REFRIGERATE as crystallisation may occur. The solution must be clear at the time of use.

DOSAGE:

• Adenosine injection should be given as a rapid bolus by the peripheral IV route. It should be given as close to the patient as possible and followed by a rapid saline flush (this is best achieved by using a three-way tap system) The recommended IV doses for adults are as follows: Initial dose: 6 mg given as a rapid IV bolus (administered over a 1-2 second period). Repeat administration: If the first dose does not result in elimination of the supraventricular tachycardia within 1-2 minutes, 12 mg should be given as a rapid IV bolus. This 12 mg dose may be repeated a second time if required. Central venous administration of adenosine has not been systematically studied; however, in the ICU setting this route of administration is acceptable.

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

• No dosage adjustment is required in renal failure or renal replacement therapy.

DOSAGE IN PAEDIATRICS:

• Paediatric Patients with a Body Weight < 50 kg:
  • Initial dose: Give 0.05 to 0.1 mg/kg as a rapid IV bolus given either centrally or peripherally. A saline flush should follow.
  • Repeat administration: If conversion of PSVT does not occur within 1-2 minutes, additional bolus injections of adenosine can be administered at incrementally higher doses, increasing the amount given by 0.05 to 0.1 mg/kg. Follow each bolus with a saline flush. This process should continue until sinus rhythm is established or a maximum single dose of 0.3 mg/kg is used.
• Paediatric Patients with a Body Weight > 50 kg: Administer the adult dose.

CLINICAL PHARMACOLOGY:

• Adenosine slows conduction time through the A-V node, can interrupt the reentry pathways through the AV node, and can restore normal sinus rhythm in patients with paroxysmal supraventricular tachycardia (PSVT), including PSVT associated with Wolff- Parkinson-White Syndrome. Intravenously administered adenosine is rapidly cleared from the circulation via cellular uptake, primarily by erythrocytes and vascular endothelial cells. Adenosine has a half- life of less than 10 seconds in whole blood.

CONTRAINDICATIONS:

1. Second- or third-degree A-V block (except in patients with a functioning artificial pacemaker).
2. Sinus node disease, such as sick sinus syndrome or symptomatic bradycardia (except in patients with a functioning artificial pacemaker).
3. Known hypersensitivity to adenosine.

WARNINGS

• Heart Block: Adenosine injection exerts its effect by decreasing conduction through the A-V node and may produce a short lasting first-, second- or third-degree heart block. Appropriate therapy should be instituted as needed. Patients who develop high-level block on one dose of adensoine should not be given additional doses. Because of the very short half- life of adenosine, these effects are generally self-limiting.
• Asystole and VF: Transient or prolonged episodes of asystole have been reported with fatal outcomes in some cases. Rarely, ventricular fibrillation has been reported following adenosine administration, including both resuscitated and fatal events. In most instances, these cases were associated with the concomitant use of digoxin and, less frequently with digoxin and verapamil. Although no causal relationship or drug-drug interaction has been established, adenosine should be used with caution in patients receiving digoxin or digoxin and verapamil in combination.
• Arrhythmias at Time of Conversion: At the time of conversion to normal sinus rhythm, a variety of new rhythms may appear on the electrocardiogram. They generally last only a few seconds without intervention, and may take the form of premature ventricular contractions, atrial premature contractions, sinus bradycardia, sinus tachycardia, skipped beats, and varying degrees of A-V nodal block. Such findings are seen in 55% of patients.
• Bronchoconstriction: Adenosine has been administered to a limited number of patients with asthma and mild to moderate exacerbation of their symptoms has been reported. Adenosine should be used with caution in patients with obstructive lung disease or asthma. Adenosine should be discontinued in any patient who develops severe respiratory difficulties.

PRECAUTIONS

• General: See CONTRAINDICATIONS and WARNINGS

IMPORTANT DRUG INTERACTIONS FOR THE ICU

• Digoxin with or without verapamil use may be rarely associated with ventricular fibrillation when combined with adenosine (see WARNINGS).
• The effects of adenosine are antagonised by methylxanthines such as caffeine and theophylline. In the presence of these methylxanthines, larger doses of adenosine may be required or adenosine may not be effective.
• Adenosine effects are potentiated by dipyridamole (persantin). Thus, smaller doses of adenosine may be effective in the presence of dipyridamole.
• Carbamazepine has been reported to increase the degree of heart block produced by adenosine.

ADVERSE REACTIONS

• The half-life of adenosine is less than 10 seconds. Thus, adverse effects are generally rapidly self-limiting.
• Body as a Whole: Apprehension
• Cardiovascular System: Facial flushing, headache, sweating, palpitations, chest pain, hypotension
• Respiratory System: Bronchospasm, shortness of breath/dyspnea, chest pressure
• Digestive System: Nausea, metallic taste, tightness in throat, pressure in groin.
• Nervous System: Lightheadedness, dizziness, tingling in arms, numbness, blurred vision, burning sensation

• 
  

http://lifeinthefastlane.com/book/critical-care-drugs/adenosine/

Ask Questions

He who asks a question may look momentarily stupid

but he who does not will remain forever ignorant 

Chinese Proverb

Blood pressure & hemodynamics

Overview of Circulation

Arterial Pressure

constant capillary flow keeps gas exchange constant and also prevents "sludging" of red cells in capillaries.  Blood is like ketchup - hard to start flow when flow is stopped.

Mean arterial pressure (MAP) is calculated as 2/3 diastolic + 1/3 systolic. 120/90 MAP = 60 + 40 = 100 mmHg.  120/80 MAP = 53 + 40 = 93 mmHg.  The reason MAP is not the average of systolic and diastolic is due to the fact that, at rest, 2/3 of the time is spent in diastole and 1/3 is spent in systole.

pulse pressure = systolic - diastolic  changes with stroke volume & aortic compliance

Control of diastolic pressure

1. heart rate  - determines "run off" time during diastole
2. total peripheral resistance (TPR) - determines slope of "run off"

MEMORY TOOL - PQR  (ABC rule)

P = QR   (use algebra to rearrange)

very useful in understanding hypertension and hypotension (shock)

R = P/Q   for whole system

R = 8nl/pi r4         for single tube   2^4 = 16

where n is viscosity; l is length; and r is radius.  Viscosity is greater with more red blood cells.  More red cells (higher Hct) = more O2 delivery but higher resistance.

There is an optimum Hct (or hemoglobin) that is close to normal Hct.  this can go up and down with blood volume

Resistance is in series; e.g. right heart and left heart or parallel; e.g., organs of body AND  capillary beds.

adding a resistance in parallel ALWAYS lowers total resistance.

e.g.,  1/R = 1/2 +1/2 +1/2 = 3/2  so R = 2/3 = .66

added R

1/R = 1/2 +1/2 +1/2 + 1/2 = 4/2  so R = 2/4 = .5

Flow = velocity x cross-sectional area

cm3/min = cm/min x cm2/min  

student question: does density change in blood to change Reynold's No.?  N = pdv/n

ans. =  no

note that in air, changes in density can be important  (why deep divers use helium),  Helium also used clinically in patients with severe airway obstruction.

Regulation of Blood Pressure  P = QR

R

slow = hormonal

fast = neural

Q

slow = hormonal

fast = neural

Cardiac Cycle

tricuspid valve   then    bicuspidvalve   memory tool:  "try it before you buy it"

Wiggers Diagram with EKG

Right heart pressures LOW due to lower resistance of lung circulation.

Importance of low right atrial pressure  = avoids edema in organs and peripheral circulation.  Sign of right heart failure = peripheral edema (e.g., swollen ankles)

Pharmacology of EKG

Pharmacology of EKG 

Class IA

e.g. procainamide, quinidine

block Na channels and K channels

drug interactions

• diuretics, steroids, amphotericin B = K loss
• low K interferes with phase 3 K efflux (K channels require bound K to function normally.
• other drugs
• tricyclic antidepressants

Class IB

e.g., lidocaine

• works on cells with long action potentials = ventricles, not atria
• little or no effect on QRS or AP  (nl EKG)

drug interactions

Hyperkalemia - lidocaine  increases chance of toxicity  

Class IC
e.g., flenainide

• effects on EKG similar but smaller than IA.
• works on both atria and ventricles

Local Regulation of Blood Flow

Local Regulation of Blood Flow

• autoregulation - most important in kidney, heart, and brain (not in lung)
• MECHANISM = matching R and P to keep Q constant  
• Q = P/R
• myogenic reflex  (stretch activated channels if P is high; K channel activation if P is low)
• range over which autoregulation occurs may change;e.g., chronic hypertension shifts range to higher values.

• metabolic regulation

• In Lungs hypoxia has opposite effect = vasoconstriction - mediated by specializes K channels that are inhibited by hypoxia = depolarization and Ca influx.

• Flow regulation
• hemodynamic forces

Pulmonary Edema

Pulmonary Edema





It is less confusing to think of the colloid osmotic pressure as a positive number with a minimum value of zero (NO PROTEIN).





When the rate of fluid filtration from the capillary 
into the interstitium is the rate of lymphatic removal and evaporation - no net fluid accumulation.


• However, when the rate of fluid filtration from the 
capillary into the interstitium is > the rate of lymphatic removal and evaporation - there is net 


fluid accumulation PULMONARY EDEMA.



Cardiogenic Pulmonary Edema



In a normal lung, the driving force for fluid filtration is 
~1 mmHg

• If in CHF the pulmonary capillary pressure increases 
to ~25 mmHg

• Assuming that at least initially Pi ~ 8 mmHg, plasma 
protein osmotic pressure is ~28 mmHg, interstitial 

fluid protein osmotic pressure is ~14 mmHg, and 
remains 0.98

• Then [(25 8) 0.98(28 14)] = ~ 19 mmHg






Treatment for pulmonary edema


Decrease Preload: diuretics, sit patient up in bed, n
itrates, morphine, dialysis.
Improve Cardiac Performance: Nitrates, Inotropes, 
Digoxin.
Decrease Afterload: ACE inhibitors, nitroprusside
Increase Pi: Continuous positive airway pressure, 
mechanical ventilation
Decreasing LpA, or osmotic pressure has not been 
attempted.
Non-cardiogenic Pulmonary Edema

If there is endothelial damage Lp
increases and Jv increases





Capillary endothelium loses barrier function
– Does not require change in hemodynamics
– Forces that oppose Pc decrease
– LpA increases
– leaky capillaries and increased fluid filtration!

Treatment of non-cardiogenic pulmonary edema


Treatment / Removal of offending source (infection , aspiration , inhalation)
• Mechanical Ventilation if necessary (with low tidal volumes)
• Many experimental therapies (antiinflammatory among others)


DDx Cardiogenic versus Non-cardiogenic


Underlying condition: Myocardial infarction vs. severe infection
• X-ray appearance
• Estimates of Pc (central venous pressure, BNP peptide)
• Measurement of Pc (Swann-Ganz Catheter)
• Measurement of Alveolar protein concentration (estimate of πi)


Hanta virus = both cardiogenic and non-cardiogenic pulmonary edema

High altitude pulmonary edema (HAPE)

cardiogenic = pulm venoconstriction
non-cardiogenic = protein in alveolar fluid

Pulmonary Edema

into the interstitium is the rate of lymphatic 

Treatment for pulmonary edema

• Decrease Preload: diuretics, sit patient up in bed, n
  • itrates, morphine, dialysis.
• Improve Cardiac Performance: Nitrates, Inotropes, 
  • Digoxin.
• Decrease Afterload: ACE inhibitors, nitroprusside
• Increase Pi: Continuous positive airway pressure, 
  • mechanical ventilation
• Decreasing LpA, or osmotic pressure has not been 
  • attempted.

Non-cardiogenic Pulmonary Edema

If there is endothelial damage Lp

increases and Jv increases

Capillary endothelium loses barrier function

– Does not require change in hemodynamics

– Forces that oppose Pc decrease

– LpA increases

– leaky capillaries and increased fluid filtration!

Treatment of non-cardiogenic pulmonary edema

Treatment / Removal of offending source (infection , aspiration , inhalation)
• Mechanical Ventilation if necessary (with low tidal volumes)
• Many experimental therapies (antiinflammatory among others)


DDx Cardiogenic versus Non-cardiogenic


Underlying condition: Myocardial infarction vs. severe infection
• X-ray appearance
• Estimates of Pc (central venous pressure, BNP peptide)
• Measurement of Pc (Swann-Ganz Catheter)
• Measurement of Alveolar protein concentration (estimate of πi)


Hanta virus = both cardiogenic and non-cardiogenic pulmonary edema

High altitude pulmonary edema (HAPE)

• cardiogenic = pulm venoconstriction
• non-cardiogenic = protein in alveolar fluid

Potassium homeostasis

Potassium

Potassium Space is Huge

• NaK ATPase constantly bailing Na to keep K inside
• K "bath" used to stop hearts for surgery
• diarrhea loss can be much higher than nl (up to 100 mEq/day)
• creates metabolic acidosis with hypokalemia  (in most cases acidosis comes with hyperkalemia)

K homeostasis

• rhabdomyolysis may cause dangerous hyperkalemia

Physiology of K homeostasis

Death by avocado  -  response to K intake

alpha intercalated cells and principal cells fine tune the 13% of K+ that remains in the tubule after reabsoption by the proximal convoluted tubule and thick ascending limb of the loop of Henle.  alpha cells reabsorb K+ if there is hypokalemia.  principal cells secrete K+ if there is hyperkalemia.  Also, the principal cells are the target of the adrenal medulla hormone, aldosterone, which increases Na+ reabsorption and K+ excretion.

There appears to be a well-developed system for sensing potassium by the pancreas and adrenal glands. High potassium states stimulate cellular uptake via insulin-mediated stimulation of sodium-pump activity in muscle and stimulate potassium secretion by the kidney via aldosterone-mediated enhancement of distal renal expression of secretory potassium channels (ROMK).

Low potassium states result in insulin resistance, impairing potassium uptake into muscle cells, and cause decreased aldosterone release, lessening renal potassium excretion. This system results in rapid adjustments in immediate potassium disposal and helps to provide long-term potassium homeostasis.

Na and K levels Interact  --  Edelman equation

Plasma [Na +] = Na+ + K+/TBW

Kidneys reabsorb all filtered load of K (720 mEq/day) - most in collecting duct (principal cells)

Bartter's Syndrome  - thick ascending limb  = same effect as loop diuretics

Gittleman Syndrome - DCT - resembles thiazide diuretic

Potassium sparing diuretics

• amiloride - Naa channel blocker
• reduced aldosterone (ACE inhibitors) or aldosterone receptor blockers (spinolactone)