High Yield Relationships—Slide # 1

P L
Q= MAP = CO X TPR CO = HR X SV P ∝ R R∝
r4 SV
R PP =
Reynold’s # = (velocity) (diameter) (density) / viscosity C
Cardiac Index = CO/ body surface area (BSA) V
C=
Pulse pressure (PP) = systolic - diastolic P
MAP = 1/3 PP + diastolic pressure
T ∝ Pr
P = height X density X gravity
(LaPlace)
EF = SV/EDV X 100
Uptake of O2 (Vo2)
Velocity = Q/CSA Fick Flow =
principle A – V O2 difference
Extraction
of O2
Uptake of O2 (Vo2) = Flow X A – V O2 difference

© LBW
 Short/Long Term MAP Reg—Slide # 2
1 Contractility Veno-
1 constriction
Heart rate Autonomic
drugs  VR
M2 Stroke volume
F-S Preload
VR
Cardiac Shock TPR
output  Blood volume

Pharm/Path
Anti- Mean Arterial Urine volume
Integration
hypertensives Pressure
Renin
Short-
term reg Baroreceptor activity 
Ang II
Stimulates Parasympathetic Sympathetic
Inhibits activity Aldo
activity
© LBW
 Regulation of CO—Slide # 3
Directly
related but Directly Myocardial
HR complex related
Contractility
Cardiac
Inversely
Output
Directly
related
CAP!
related
Preload
Afterload Determines Ventricular
compliance
Directly
related
Venous Inversely
related

Blood
Return Resistance
Inversely Directly
Volume related related

Compliance Muscle pump

© LBW
 Whole Body CV Regulation—Slide # 4
MAP = CO X TPR
4 factors determine Tone of arterioles
1. HR ( CO exercise;  CO
• Sympathetic (alpha)
with tachyarrhythmias)
• Ang II
2. Contractility (direct)
• AVP (ADH)
3. Afterload (inverse)
• Epi (alpha/beta-2)
4. Preload (direct)
• Metabolism
• NO
Directly related to venous return
• Pharm integration
• Blood volume (direct)
• Venous compliance (inverse)
• TPR (inverse)
• Muscle pump
© LBW
PV Loops: Systolic/Diastolic Dysfunction—Slide # 5
Pathology Systolic dysfunction:
Integration decreased contractility
results in elevated volumes
120
Pressure (mmHg)

Diastolic dysfunction:
80 decreased compliance
causes increased
pressure

40

Passive
50 100 150 tension
Volume (ml)
© LBW
 Differential for Causes of Hypoxemia—Slide #6
Low PaO2 Note PaCO2 (may avoid
PAO2: calculate using
(hypoxemia) calculation step):
alveolar air equation or
use end-tidal PO2 If low, then NOT low
PAO2 (exception is high
A – a O2
altitude), thus go straight
gradient
to elevated gradient.
Normal Elevated

Cause is
PAO2 Increase
FIO2 Doesn’t
Corrects correct PaO2
PaO2
FIO2 corrects
PaCO2 likely Cause is right-
elevated Diffusion VA/Q to-left shunts
impairment mismatch

© LBW
 Relationships/Equations for Renal—Slide # 7

Transport = excretion – filtered load

GFR
FF = Filtered load = GFR X PX
RPF
Rate of excretion = UX X V
FF impacts Pc!!!

UPAH X V
CPAH = ERPF =
Renal UX X V PPAH
clearance =
PX
ERPF
Renal blood flow =
1- Hct

© LBW
 Factors Affecting GFR and FF—Slide # 8

Glomerular Peritubular Nephron GFR FF

cap cap plasma
pressure pressure flow
Constrict efferent
    
Dilate efferent
    
Constrict afferent
    
Dilate afferent
    

© LBW
 Properties of Receptors—Slide # 9
Biochemistry Integration: Enzyme kinetics
E + S  (ES)  E + P H + R  (HR)  response
Michaelis-Menten stimulus  response

100 100

Vmax: determined
Velocity (% of max)

[R] is one

% Response
by [E] & [S]
factor

50 50
[S] is [H] is
limiting limiting
Km

0 0
[S] [H]
© LBW
 Properties of Receptors—Slide # 10
Pharmacology Integration: Pharmacodynamics
H+R (HR) response A+R (AR) response
stimulus response stimulus response
100 100

[R] is one

% Response
% Response

factor

50 50
[H] is [A] is
limiting limiting

EC50

0 0
[H] Log [A]

© LBW
 Overview of ADH Pathophysiology—Slide # 11
High Plasma osmolality Low

Tells you ADH Note: ADH=AVP Tells you ADH

SHOULD BE HIGH SHOULD BE LOW
Plasma ADH Plasma ADH

High Low High Low

*Nephro DI
(1O)

Dehydration Neuro DI* SIADH Primary Poly-

(2O) (1O) (1O) dipsia (2O)

Uosm >> 300 Uosm << 300 Uosm >> 300 Uosm << 300
Bottom row tells you what ADH IS
© LBW
 Metabolism—Cortisol—Slide # 12
Glycogen
Gly Cortisol
synthase Gly
phos FA
Glucokinase
Glucose FA
Glucose
6-P synthase
G6-phos PFK-1 (via
Fructose 1,6- PFK-2) Malonyl CoA
AA
bisphosphatase Pyruvate (alanine)
kinase Acetyl CoA
PEPCK PDH carboxylase
OAA
(thiamine)
Pyruvate Acetyl CoA
Pyruvate
Cortisol carboxylase
(biotin) LDH

Lactate TCA Ketones

© LBW
 Insulin—Glucagon—Slide # 13
Glycogen Insulin stimulates+
Gly
synthase+ Gly Glucagon stimulates*
phos* FA
Glucokinase+
Glucose FA
Glucose
6-P synthase+
G6-phos* PFK-1 (via
PFK-2+) Malonyl CoA
Fructose 1,6- Urea
bisphosphatase* Pyruvate
kinase+ 1* Acetyl CoA
PEPCK* PDH carboxylase+
OAA
(thiamine)
Pyruvate Acetyl CoA
Pyruvate
carboxylase
(biotin) LDH
1 = N-acetylglutamate Lactate TCA Ketones

© LBW
 Sexual Differentiation—Slide # 14
MIH = Müllerian inhibiting T = Testosterone
hormone SRY = sex determining
region of Y

XX—no XY has
Ovaries SRY SRY Testes

MIH T

Müllerian Wolffian Müllerian Wolffian

ducts ducts ducts ducts

Regress Regress

Fallopian Epididymis, vas Fallopian Epididymis, vas

tubes, uterus, deferens, tubes, uterus, deferens, seminal
inner vagina seminal vesicles inner vagina vesicles

© LBW
 Sexual Differentiation—Slide # 15
5 alpha-reductase
Testosterone dihydrotestosterone (DHT)

Ovaries Testes

No DHT
DHT
Undifferentiated
organs

Clitoris, outer Penis,

vagina, labia scrotum, &
prostate

© LBW
 Menopause—Slide # 16
ACTH Path/Pharm Integration FSH/LH

Choles Tumor Choles

Growth
DHEA Test/A
aromatase
A 17b-Estradiol
Blood
Adrenal cortex Ovary
Anastrozole
Tamoxifen
Letrozole
Raloxifene

aromatase
DHEA A Estrone

Adipose tissue © LBW

 Polycystic Ovarian Syndrome (PCOS)
Pharmacology/Pathology Integration
Hirsutism; irregular menstrual bleeding; chronic anovulation; obesity;
insulin resistance; infertility
Clomiphene: FSH Oral contraceptives
LH to LH
FSH

Adipose Pituitary
estrone

Thecal
Estradiol Follicle hormone
aromatase
anovulation maturation production
Adipose
Ovaries
insulin
Androgens
Dexamethasone
Thiazolidinediones; Androgens
SHBG Metformin Spironolactone
© LBW Adrenal HO #17; Pgs 370-71