physiology slides usmle

7/30/2019 physiology slides usmle

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Angiotensinogen

Angiotensin I (AI)

Angiotensin II (AII)

(ACE)

Renin

Aldosterone (Na+

and water retention)

Primary factors regulating Renin:

1. Perfusion pressure to the kidney stimulates; inhibits

2. Sympathetic stimulation to kidney viaBeta-1 receptor

3. Na+ delivery to the macula densa delivery stimulates; delivery inhibits

Primary factors regulating aldosterone:

1. Plasma [angiotensin II] (AII) stimulatesrelease

2. Plasma [K+] stimulates releasePrimary factors regulating AVP:

1. Plasma osmolarity stimulates release

2. Blood volume/pressure

inhibits release

Integration of Volume RegulationSlide # 1

RAAS


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SummaryEdemaSlide # 2

Primary causes of edema (High yield for exam)

Pc: FlowVasodilation; Venous pressureVenousobstruction; heart failure; Blood volume (Na+ retention)Heart

failure

vascular oncotic pressure: Liver; Kidney Capillary permeability: Inflammatory response(TNF-alpha; histamine; bradykinin)

if: HypothyroidMyxedema Lymphedema: Filarial (W Bancrofti); bacterial

lymphangitis (streptococci); trauma; surgery; tumor


3/46

- +-70 mV

(Em)

[K+]OLow

[K+]iHigh

[Na+]OHigh

[Na+]iLow

[Cl-]OHigh

[Cl-]i

Low

Prot -

Prot -

Prot -

Prot -[Ca2+]iLow*

[Ca2+]OHigh

High YieldIonic EquilibriumSlide # 3

*-refers to cytosolic free calcium


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High YieldIonic EquilibriumSlide # 45 fundamental principles

1. Membrane po tential (Em ):electrical charge (voltage) across

a cells membrane.

2. Electrochemical gradient:term describing the combination

of chemical and electrical gradients driving the diffusion of ions.

3. Equi l ibr ium po tent ial :membrane potential that balanceschemical and electrical force across the membrane. In other

words, the membrane potential that results in no NET diffusion of

an ion. (Nernst equation)

4. Conduc tance (g) or permeabi l i ty:ease with which an ioncrosses the cell membrane. Determined by number of open

channels that allow the ion to pass through the membrane.

5. Driv ing force (net forc e):Resting membrane potential minus

equilibrium potential.


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Fast Sodium ChannelsSlide # 5

Open

Na+

Na+Na+

Positive membrane

potential and timeclose h-gate

h-gate

(inactivation)

M-gate

(activation)

Inactivated

Depolarization

opens M-gate

Closed at Em

Repolariztion

TTX; STX; Caine

Ca2+

Pharmacology

Integration

Tetrodotoxin (TTX)/Saxitoxin (STX)/Caine drugs

Outside

Inside

Ciguatoxin (CTX)/Batrachotoxin (BTX)


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Nerve DysfunctionSlide # 6

Alpha motor neuronSkeletal

muscle

Decreased excitability/Lack of conduction

Ion disturbances Hypokalemia ( gradient) Hypercalcemia (Na+

channels)

Demyelination

Guillain-Barr syndrome

(GBS)

Neuronal loss

ALS

Aging

Toxins/drugs

TTX/STX

Local anesthetics

Weakness; fatigue; ataxia;

hyporeflexia; paralysis; sensory deficit

Ion disturbances

Hyperkalemia

(

gradient) Hypocalcemia

(Na+ channels)

Increased excitabilityToxins/drugs 3,4-DAP; 4-AP

CTX/BTX

hypereflexia; spasms;

muscle fasciculations;tetany; tremors;

paresthesia; convulsionsCentral

demyelination

by MS


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Voltage-gated Ca2+

channel

Na+

K+

Ca2+

Na+

ACh

Nicotinic receptor Voltage-gated Na+

Depolarizing & non-

depolarizing blockers Myasthenia Gravis:autoimmune/congenital

Lambert-Eatonsyndrome:

autoimmune

Demyelination of GBS can block

action potential

AChE inhibitors

(organophosphates)

Botulinum toxin (Botox)

prevents release of ACh

Hyperkalemia/ hypocalcemia Hypokalemia/ hypercalcemia

TTX

STX

Latrotoxin

3,4-

DAP

4-AP

Neuromuscular Junction (NMJ)Slide # 7


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High Yield EKG ChangesSlide # 8

Path/Pharm

Integration

ST Elevation

Transmural infarction

Prinzmetal angina

ST Depression

Subendocardial ischemia

Classic (stable) angina

Hyperkalemia: Rate repol Sharp, spiked T wave

QT interval

Hypercalcemia

QT interval

Hypokalemia: Rate repol U waves

QT intervalHypocalcemia

QT interval


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Muscle DysfunctionSlide # 9

Alpha motor

neuron

Skeletal muscle

Decreased

force (weak) Muscular dystrophies

Disuse Atrophy

Aging

Protein wasting

Pompe

Malignant

hyperthermia (treat

with dantrolene)

Tetanus toxin

(glycine in spinal

cord)

Spasms/

contractures

Exercise-induced

McArdle

Exercise-induced

McArdle

NM block

TTX/STX

Local anesthetics

Botox

ALS

GBS

Severed nerve

Flaccidparalysis


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High Yield RelationshipsSlide # 10

Q =

DPR CO = HR X SV C = DP

DV

C

SVPP =R L

r4

T Pr

(LaPlace)

Pulse pressure (PP) = systolic - diastolic

DP R

MAP = 1/3 PP + diastolic pressure

Velocity = Q/CSA

P = height X density X

gravity

Uptake of O2

A V O2 differenceFlow =

Cardiac Index = CO/ body surface area (BSA)

Uptake of O2 = Flow X A V O2 difference

MAP = CO X TPR

Reynolds number = (velocity) (diameter) (density) / viscosity

EF = SV/EDV X 100


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Free Flow (Q)Slide # 11

P = 70P = 80

Q

DownstreamPressure

UpstreamPressure

Change R

here

Vasoconstrict

DP R


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Deeeeep

Thoughts Brain

= resistor

Arterioles are

resistors!!

Total resistance(TPR/SVR) is sum of

each resistor.

Think of each

resistor as a faucet.

Total resistance

(TPR/SVR) is

AFTERLOAD for

heart.

Must have an adequate

MAP to drive flow!!!!

P = Q X R

MAP = CO X TPR

Slide # 12

Cant have all

faucets open

simultaneously.

Vasoconstrictors

Sym (NE)alpha!!! Epialpha

AII & AVP

Alpha agonists

NE releasers

Reuptake blockers

Vasodilators

sym!!! EpiBeta-2

metabolism & NO Alpha blockers

NO releasers

CCB

K+ channel


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Low

Compliance

Water

ComplianceSlide # 13

DV = DP X C

High

Compliance

DP = CDV

C = DPDV

Water


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Venous Return is the flow of blood TO the heart.

Central blood volume is directly related to venous return.

Central blood

volume

(PRELOAD)

CVP and pulmonary wedge pressure are clinical markers ofcentralblood volume

Venous return is

DIRECTLY related to

blood volume and

INVERSELY relatedto venous

compliance

Blood volume in?Sympathetic stimulation

compliance, thus venous return

Pharm Integration:

Nitrates preferentially

dilate veins ( theircompliance)

What does an elevated CVP suggest?

Pump failure

Venous ReturnSlide # 14

Venous

return

blood volume; Venoconstriction


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MAP = CO X TPR

4 factors determine

1. HR ( CO exercise; COwith tachyarrhythmias)

2. Contractility (direct)

3. Afterload (inverse)

4. Preload (direct)

Directly related to venous return

Blood volume (direct)

Venous compliance (inverse)

Tone of arterioles

Sympathetic (alpha)

AII AVP

Epi (alpha/beta-2)

Metabolism

NO

Pharm integration

Whole Body CV RegulationSlide # 15


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Effect of GravityCompensationsSlide # 16

Venous Pooling

ventricular volume(sensed by cardio-

pulmonary

baroreceptors)

Reflex sympatheticnervous system

Sympathetic activation:

Constricts veins (Rec?)

HR/Inotropy (Rec?) Constricts arterioles (TPRRec?)

Path/PharmIntegration

Orthostatic intolerance

vascular volume Venodilators; alpha blockers

Denervated heart/ heart failure

Dysautonomias (diabetes mellitus)

Arterial baroreceptorsif MAP falls


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Anti-hypertensive

drugs

Short/Long Term MAP RegSlide # 17

Mean Arterial

Pressure

InhibitsStimulates

Baroreceptor activity

Sympathetic

activity

Contractility

TPRCardiac

output

Heart rateb1

a

b1 Veno-constrictiona

Stroke volumePreload

M2

Parasympathetic

activity

Urine volume

Blood volume

Renin

A II

b

VR

VRF-S

Aldo

Shock

Autonomic

drugs


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High Yield Application of Fick Principle

Cvo2Cao2Q

Cell

consumes

O2

VO2 = Q X (CaO2 CvO2)

Fick

O2 delivery = Q X CaO2

Q Extraction Venous O2 CaO

2with same Q & extraction Venous O

2

O2 extraction (by

the tissue)

O2

consumption

Slide # 18For any given O2

consumption, a

indelivery results in: 1)

possible hypoxic/ischemic

damage, & 2) a theamount of O2 in the veins

draining the tissue.


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Tip 2: Pressure/volume behind the defective valve

Systolic murmur: Mitral/Tricuspid insufficiency;

Aortic/Pulmonic stenosis Diastolic murmur: Mitral/Tricuspic stenosis;

Aortic/Pulmonic insufficiency

Stenosis: Narrowed opening through valve. Bottom

line is increased resistance to outflow. Murmur when open

Insufficiency (also called regurgitant and/or

incompetent): Valve fails to close properly. Bottom line is

backflow of blood occurs. Murmur when closed

Tip 1: Think of when valve is open and closed

Valvular ProblemsSlide # 19

F A ti th R i t S t Slid #20


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Forces Acting on the Respiratory SystemSlide #20

Key forces to be aware of to understand ventilation

Chest wall recoil: Force exerted by the chest wall; At rest,

this is an OUTWARD force.

Intrapleural pressure (IPP): Fluid pressure in the intrapleural

space. It is the OUTSIDE pressure for the alveoli, airways, and

blood vessels within the chest.

Transmural (PTM) pressure gradient: Pressure gradient

across alveoli and small airways (see handout, slide #21)

Lung recoil: Force exerted by the alveoli; This is an INWARD

force and is inversely related to compliance.

T l P G di t Slid # 21


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Transmural pressure (PTM) gradient is the pressure

gradient across the wall of any tube or sphere.

PTM

= Pi

- Po

Po

Transmural Pressure GradientSlide # 21

Pi

Alveolus, airway, or blood vessel

IPP P l Bl d Fl Slid # 22


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Pg 147

IPPPulmonary Blood FlowSlide # 22

Inspiration

PTM = 0-5 = 5

Becomesmore

negative

RA in chest expands pressure so Q (VR)

Increased output delays

closing of pulmonic valve

(physiologic splitting of S2

)

PTM forpulmonary

vessels; their

volume increases

Increases pulmonary

vascular resistance

Flow to LH

MAP = CO X TPR

Inspiration decreases vagal outflow

to the heart, thus HR increases

(respiratory sinus arrhythmia)

Veins here are

unaffected

S V /Q Mi t h Slid # 23


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Severe VA/Q MismatchSlide # 23

1. Increased A a gradient

2. Increasing FIO2 helpful

Diagnostic signs:

PAO2 = (Patm 47) FIO2 (PACO2/R)

Flow from low VA/Qunits (


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Differential for Causes of HypoxemiaSlide # 24

Low PaO2

(hypoxemia)

A a gradient

FIO2 corrects

PaCO2 likely

elevated

Normal

Cause is

PAO2

Elevated

Increase FIO2

Doesnt

correct PaO2

Cause is right-

to-left shunts

Corrects

PaO2

VA/Q

mismatch

Diffusion

impairment

PAO2: calculate usingalveolar air equation or

use end-tidal PO2

H i Slid # 25


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HypoxemiaSlide # 25

PAO2: Obstructive disease; Drug overdose; Anesthesia; Altitude;Chest restriction, e.g., kyphoscoliosis

Diffusion Impairment: Restrictive disease (pulmonary fibrosis);

Pulmonary edema (ARDS, Left ventricular failure)

VA/Q mismatch: Severe obstruction (Status asthmaticus, Cystic

fibrosis, anaphylaxis); Infection (pneumonia); Partial occlusion

from mucus plugs

Shunts: Atelectasis (pneumothorax; ARDS); complete occlusion

of an airway (mucus plug, foreign object); TOF

R l ti hi /E ti f R l Slid # 26


26/46

Relationships/Equations for RenalSlide # 26

GFR

RPF

FF =

FF impacts Pc!!! Filtered load = GFR X PXRate of excretion = UX X V

Transport = excretion filtered load

Renal

clearance =UX X V

PX

UPAH X VCPAH =

PPAH

ERPF =

Renal blood flow =1- Hct

ERPF

F t Aff ti GFR d FF Slid # 27


27/46

Factors Affecting GFR and FFSlide # 27

Glomerularcap

pressure

Peritubularcap

pressure

Nephronplasma

flow

GFR FF

Constrict efferent Dilate efferent Constrict afferent Dilate afferent

U i A id Slid # 28


28/46

Uric AcidSlide # 28

Pharmacology

Integration

Adenosine

Guanosine

Hypoxanthine

Guanine

Salvage

Xanthine

Uric Acid H+ + Urate-

Xanthine

Oxidase

Urate-

Urate-

Urate-Allopurinol

Biochemistry

IntegrationProbenecid

Lesch-Nyhan

80-90% of

urate isreabsorbed

in PT

UA

+

Precipitate

At low

tubular

pH

Gout

X

Ele ated Anion Gap MUDPILES Slide # 29


29/46

Elevated Anion GapMUDPILESSlide # 29

L: Lactic acidosis

E: Ethylene glycol; Ethanol ketoacidosis

S: Salicylates; starvation ketoacidosis; sepsis

I: Iron; Isoniazid

U: Uremia (renal failure)

D: Diabetic ketoacidosis

P: Paraldehyde

M: Methanol

Normal Anion Gap HARD UP Slide # 30


30/46

Normal Anion GapHARD UPSlide # 30

P: Pancreatic drainage (pancreatic fistula)

U: Ureteral diversion (ureterosigmoidostomy)

A: Acetazolamide

R: Renal tubular acidosis

D: Diarrhea

H: Hyperchloremia (Parental nutrition)

Acid Base Decision Tree Slide # 31


31/46

Acid-Base Decision TreeSlide # 31

Compensation?

Osis?

(pH)

Compensation?

Cause of

the osis?

ACIDOSIS ALKALOSIS

NOTE: Paco2 in resp acidosis; compensatory metab alkalosis (compute Paco2)

NOTE: Paco2

in resp alkalosis; compensatory

metab acidosis (compute Paco2)NOTE: Calculate anion gap: [Na+ - (Cl- + bicarb)]

Low

(Acidosis)

High

(Alkalosis)

Low Elevated

Respiratory MetabolicMetabolic Respiratory

Use Winters to

determine what

Paco2 should be

Determine if

acute (1:0.2) or

chronic (1:0.4)

Determine if

acute (1:0.1) or

chronic (1:0.4)

Paco2 0.7 torrfor every 1 mEq/L

in bicarb

Look at bicarb

Cause of

the osis?

Low Elevated

Look at bicarb

Properties of Receptors Slide # 32


32/46

50

100

0[H]

%R

espons

e

E + S (ES) E + P H + R (HR) responsestimulus response

50

100

0[S]

Velocity(%o

fmax)

Michaelis-Menten

Km

Vmax: determined

by [E] & [S]

Properties of ReceptorsSlide # 32

[H] is

limiting

[S] is

limiting

[R] is onefactor

Properties of Receptors Slide # 33


33/46

50

100

0Log [A]

%R

esponse

50

100

0[H]

%R

esponse

Properties of ReceptorsSlide # 33

H + R (HR) responsestimulus response A + R (AR) responsestimulus response

EC50

[H] is

limiting

[H] is

limiting

[R] is onefactor

Overview of AVP Pathophysiology Slide # 34


34/46

Overview of AVP PathophysiologySlide # 34

Low

Dehydration(2O)

High

Primary Poly-dipsia (2O)

SIADH(1O)

Plasma AVP

POSM

UOSM< 1

POSM

UOSM> 1

LowHigh

LowHigh

Plasma osmolality

*Nephro DI

(1O)

Plasma AVP

POSM

UOSM< 1

POSM

UOSM> 1

Neuro DI*(1O)

Note: AVP=ADH

Metabolism Cortisol Slide # 35


35/46

MetabolismCortisolSlide # 35

Glucose

G6-phos

Glucose

6-P

Glucokinase

Glyphos

GlycogenGly

synthase

PEPCK

Fructose 1,6-

bisphosphatase

PDH

(thiamine)

Acetyl CoAPyruvate

carboxylase

(biotin)

OAA

Lactate

LDH

Acetyl CoA

carboxylase

Malonyl CoA

TCA Ketones

FA

FA

synthase

Pyruvate

kinase

PFK-1 (via

PFK-2)

Pyruvate

AA

(alanine)

Cortisol

Cortisol

Insulin Glucagon Slide # 36


36/46

Glucose

G6-phos

Glucose

6-P

Glucokinase

Glyphos

GlycogenGly

synthase

PEPCK

Fructose 1,6-

bisphosphatase

PDH

(thiamine)

Acetyl CoAPyruvate

carboxylase

(biotin)

OAA

Acetyl CoA

carboxylase

Malonyl CoA

TCA Ketones

FA

FA

synthase

Pyruvate

kinase

PFK-1 (via

PFK-2)

Pyruvate

AA

(alanine)

Insulin stimulates

Glucagon stimulates

InsulinGlucagonSlide # 36

Urea

Diabetes Mellitus Slide # 37


37/46

Pharmacology Integration: Type II diabetes

GI tract Blood Glucose

Pancreas: Secretes

Insulin

Liver

Sulfonylureas

Acetohexamide

TolbutamideChlorpropamide

Glipizide

GlyburideGLP-1 analogs

Exenatide

Acarbose

X

Thiazolidinediones

Pioglitazone

RosiglitazoneGI

problems

Hypoglycemia

DPP-IV inhibition

Sitagliptin

(+)

Uptake

Skeletal

muscle

Adipose

Uptake

Metformin

(-)

(-)Metformin

(+)

(+)

(+)

Diabetes MellitusSlide # 37

Calcium Regulation Slide # 38


38/46

Pg 316

Calcium RegulationSlide # 38

Inhibits

Stimulates

Plasma Ca2+Plasma

phosphate

Renal Ca2+

reabsorption

Ca2+ mobilization

from bone

Ca2+ absorptionfrom GI

PTH

7-dehydro-

cholesterol

25-(OH)-D3

1,25-(OH)2-D3

excess

1-hydroxylase

in kidney

Renal phosphate

reabsorption

25-hydroxylase

in liver

GI phosphateabsorption

H+

Cortisol

Estrogen *

Sexual Differentiation Slide # 39


39/46

Sexual DifferentiationSlide # 39

Wolffian

ducts

Mllerian

ducts

Wolffian

ducts

Mllerian

ducts

Fallopian

tubes,

uterus, inner

vagina

Epididymis,

vas

deferens,

seminalvesicles

Epididymis,

vas

deferens,

seminalvesicles

T = Testosterone

SRY = sex determiningregion of Y

MIH = Mllerian inhibiting

hormone

Ovaries

Fallopian

tubes,

uterus,

inner vagina

XY has

SRY

XXno

SRY Testes

TMIH

Regress Regress

Undifferentiated

gonad



40/46


Ovaries Testes

Undifferentiated

organs

DHT

Clitoris, outer

vagina, labia

Penis,

scrotum, &

prostate

No

DHT

Testosterone dihydrotestosterone (DHT)5 alpha-reductase

MenopauseSlide # 41


41/46

MenopauseSlide # 41

Test/A

17b-Estradiol

CholesCholes

Adipose tissue

Adrenal cortexBloodA

DHEA

FSH/LHACTH

aromataseEstrone

aromatase

Ovary

DHEA A

TumorGrowth

Anastrozole

LetrozoleTamoxifen

Raloxifene

Polycystic Ovarian SyndromeSlide # 42


42/46

Polycystic Ovarian SyndromeSlide # 42

PCOSHirsutism; irregular menstrual bleeding; chronic anovulation; obesity;

insulin resistance; infertility

Thecalhormone

production

Adipose estrone

LH

FSHPituitary

Folliclematuration

aromatase Estradiolanovulation

Androgens

Adrenal

Adipose Ovaries

Androgens

Oral contraceptives

to LH

Thiazolidinediones;

Metformin

insulin

SHBG

Clomiphene: FSH

Dexamethasone

Venous PulseSlide # 43


43/46


No atrial contraction

Pathology

Integration

Atrial pressure

Atrial

contraction

PR interval

Text on

pg 124

by stiff right ventricle: Pulm Sten;Pulm regurg



44/46


Atria relax

Pathology

Integration

Bulging of

the tricuspidText on

pg 124



45/46

Venous Pulse Slide # 45

Pathology

Integration

Filling of the

atria

Enhanced because of

backflow of blood

Text on

pg 124



46/46

Venous Pulse Slide # 46

Pathology

Integration

Blunted because

of resistance

Enhanced because of

atrial engorgement

y-decent is

associated

with emptyingof right atrium

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