Cardiovascular System

■ Circulation
■ pulmonary vs
systemic
■ Ventricles (Right vs Left)
■ thickness
■ force
■ pressure
■ work
■ afterload
■ SV and Heart rate
■ CO
CARDIAC VALVES

■ responsible for the

unidirectional flow
of blood
■ movement is passive
■ AV valve
■ SL valve
 BLOOD SUPPLY

Myocardial O2 and nutrient supply Myocardial O2 and nutrient demand

(Coronary blood flow) wall stress
duration of diastole (thickness, pressure and volume)
perfusion pressure heart rate
vascular resistance contractility
Ischemic Heart Disease (IHD)
■ a condition in which
there is an inadequate
supply of blood and
oxygen to a portion of
the myocardium.
■ due to imbalance between
myocardial oxygen
supply and demand
■ most commonly due to
atherosclerotic disease of
coronary arteries
Taken from: Simple Health Secrets images
 PATHOPHYSIOLOGY
EXERCISE
ENDOTHELIUM DAMAGE SYMPATHETIC DISCHARGE
ATHEROSCLEROSIS (Dyslipidemia)
D emand
Myocardial O2
supply
Myocardial O2 Determinants of Myocardial O 2
Demand/Requirement (75%)
Determinants of Myocardial Wall Stress (ABP)
O 2 Supply (Coronary blood Intraventricular pressure
flow) Ventricular volume (radius)
Perfusion Pressure (aortic Ventricular wall thickness
diastolic pressure) Heart rate
Duration diastole Contractility
Vascular resistance

MYOCADIAL TISSUE ISCHEMIA

↓ OXYGEN DEMAND
BETA BLOCKERS
↑ OXYGEN SUPPLY ACCUMULATION OF TISSUE METABOLITES CALCIUM CHANNEL
VASODILATORS BLOCKERS
Nitrates VASODILATORS
Calcium Blockers DRUGS THAT BLOCK LATE
LIPID LOWERING AGNETS SODIUM CURRENT
ANGINA PECTORIS FATTY ACID OXIDATION
(MYOCARDIAL INFARCTION) INHIBITORS
 CARDIAC MUSCLE CELLS
■ are excitable cells
■ can transmit action
potential along their
membrane
■ convert chemical energy
into a mechanical response
■ inherent ability to intrinsically
generate rhythmic action
potential without external stimuli
Physiologic Properties of Muscle Cells
❖ IRRITABILITY OR EXCITABILITY
(Bathmotropic Effect)
❖ CONDUCTIVITY (Dromotropic Effect)
❖ CONTRACTILITY (Inotropic Effect)
❖ AUTOMATICITY / RHYTHMICITY
(Chronotropic effect)
■ Automaticity (ability to initiate its own beat)
■ Rhythmicity (regularity of pacemaking ability)
 Myocardial cell Specialized for
Excitation and Conduction

■ Sinoatrial node (SA node)

■ Atrioventricular node (AV node)
■ Bundle of His
■ Purkinje fibers
CARDIAC INNERVATION
A. Intrinsic Innervation
▪ from the conducting system of the

heart

B. Extrinsic Innervation
▪
from the autonomic nervous
system
Ionic Basis of Ventricular Action Potential

X X
Tetrodotoxin Calcium Antagonist X
Class I anti- or Blockers
Arrhythmic drugs PotassiumBlockers
 Atrial muscle fibers

Ventricular muscle fibers

Bundle of His

Purkinje fibers

FAST RESPONSE
or
FAST FIBERS
SA node
AV node

SLOW RESPONSE
or
SLOW FIBER
 TYPES FAST RESPONSE SLOW RESPONSE

Atrial , Ventricular , Nodal Fibers

Examples Purkinje and Bundle of (Sinoatrial and
His Atrioventricular node)
Magnitude of Resting Greater Lesser
Membrane Potential Stable Unstable
(RMP)
Phase 0, 3 and 4
Phases Phase 0, 1, 2, 3 and 4 Phase 1 (absent) and 2 (not
prominent)
Slope of upstoke (Phase 0)
Amplitude of AP Greater Lesser
Overshoot of AP

Propagation of Action Faster Slower

Potential
Susceptibility to
conduction block Lesser Greater
 Electrophysiology of Normal
Cardiac Rhythm
SA NODE
(60 - 100bpm)

ATRIA AV NODE
(slow conduction)

BUNDLE OF HIS

PURKINJE FIBERS

VENTRICLES
!15
 Arrhythmia
deviation of cardiac
depolarization which
Taken from: static.sharecare.com

causes an abnormality in;

the site of origin of the

impulse

its rate and regularity

its conduction
Taken from: heatlhtipsinsurance.com
Anti arrhythmic Drugs
Aim of therapy is;

to reduce pacemaker activity

modify conduction or refractoriness in reentry circuits (to disable circus

movement)

Classes

Class I (Sodium Channel Blockers)

Class II (Beta Adrenergic Blockers)

Class III (Potassium Channel Blockers and agents that prolong effective refractory period)

Class IV (Calcium Channel Blockers)

 HEART BLOCKS
■ Incomplete Heart Block
■ when conduction between the atria and the ventricles
is slowed but not completely interrupted.
■ Types
■ First Degree Heart Block
■ Second Degree Heart Block
 530 SECTION V Cardiovascular Physiology

530 530 SECTION V Cardiovascular Physiology

Cardiovascular Physiology

HEART BLOCKS
SECTION V

TION ■ First Degree Heart Block

V Cardiovascular Physiology

■ all atrial impulses reach the PR = 0.16 s

Normal complex
ventricles but the PR interval
PR = 0.16 s
PR = 0.16 s
PR = 0.38 s
is abnormally long. Normal complex
Normal complex
First-degree heart block
First-

■ Second Degree
PR = 0.16 s
Heart Block PR = 0.38 s
■ not allNormal
atrialcomplex
impulses are aVF
First-degree heart block

Second-degree heart block

conducted aVF to the ventricles aVF
(2:1 heart block)
Second-degree
aVF heart block Second-degree
aVF
■ ventricular beat(2:1 may
heartfollow
block) (Wenckebach p
Second-degree heart block
every second or third atrial (2:1 heart block)
F aVF
beat. heart block
Second-degree Second-degree heart block
(2:1 heart block) (Wenckebach phenomenon)
■ “Wenckebach Phenomenon”
Taken from: Review of Medical Physiology, 24th edition
aVF
 Normal complex First-de
PR = 0.16 s PR = 0.38 s
Normal complex First-degree heart block

aVF aVF

HEART BLOCKS Second-degree heart block

(2:1 heart block)

■ Complete Heart Block aVF

heart block Second-degree heart block
block) ■ a. k. a. Third Degree Heart (Wenckebach phenomenon)
Block
aVF
■ when conduction from the Complete heart block. Atrial rate, 107; ventricular rate, 43

atria to the ventricles is

completely interrrupted.
FIGURE 2911 ECG with heart block. Individual traces that depict various forms of
leads are noted. See text for further details.
■ ventricles beat at a slow

rate independently of the

atria. and this is why the SA node normally V5 controls the heart rate. every third a
ock. Atrial ■rate, 107; ventricular rate, 43 conduction from the atria to the ventricles
When V6 is com- form of incom
Types pletely interrupted, complete (third-degree) heart block of beats in wh
Two V leads in left
■ AV nodal block results, and the ventricles beat at a low rate (idioventricular ventricular be
bundle
rhythm) independently of the atria branch
(Figure 29–11block
). The block PR interval o
■ Infranodal blockmay be due to disease in the AV node (AV nodal block) or is usually nor
ock. Individual traces that depict various forms of heart
system block arenode
shown. Whenblock) appropriate,
Taken from: Review of Medical Physiology, 24th edition
in the conducting below the (infranodal . unipo
Sometim
CARDIAC CYCLE
➢ cardiac events that occur from
the beginning of one heartbeat
to the beginning of the next.

↓ duration → ↑ heart rate

↑ duration → ↓ heart rate
 Diastole
■ Isovolumetric relaxation phase
■ Ventricular filling phase
■ rapid ventricular filling phase

■ reduced ventricular filling phase

 SYSTOLE
■ Isovolumetric contraction phase
■ Ejection phase
■ rapid ejection phase

■ reduced ejection phase

 120
50
 120 III

F
Left Ventricular Pressure (mmHg)

D
80

one
cardiac
cycle
IV
II

60

C
A
B I
0

0 50 100 150

Ventricular Volume (ml)

JUGULAR PULSES

A) a wave
▪ corresponds to atrial systole.
B) c wave
▪ produced by bulging of the tricuspid valve into the
right atrium during isovolumetric contraction.
C) v wave
▪ rise in atrail pressure before the tricuspid valve opens
HEART SOUNDS
A) Ist heart sound
▪ low pitched “lub” sound, due to closure of the AV
valves.
B) 2nd heart sound
▪ high-pitched “dub” sound, due to closure of the
SL valves.
C) 3rd heart sound
▪ due to rapid ventricular filling.
D) 4th heart sound
▪ due to atrial systole.
!30
CARDIAC OUTPUT
■ amount of blood ejected by
each ventricle per minute.
■ expressed as cardiac index
(cardiac output per body
surface area in m2)
■ right ventricle — pulmonary
circulation
■ left ventricle — systemic
circulation
Taken from: www.vascularconcepts.com
Distribution of Cardiac Output
Brain 12%

Heart 4%

Splanchnic organs 24%

Kidneys 20%

Skeletal muscles 21%

Skin and others 19%

Determinants of cardiac output

CO = SV X HR

EDV - ESV
 EFFECT OF RESPIRATION ON HEART RATE
Inspiration → ↑ heart rate
Expiration → ↓ heart rate
Bainbridge Reflex
Inspiration → ↓ ITP → ↑ venous return (right
atrium) → ↑atrial volume → (+) atrial stretch
receptors → ↑ heart rate
VENOUS RETURN
■ is the quantity of blood flowing from the
veins into the right atrium per minute.
 MCSFP - CVP
VR ------------------------------
RV

TBV - CVP
--------
VC
VR --------------------------------
RV
 Indices of Cardiac Contractility

▪ Maximum (Peak) dP/dT

▪ tangent of the upstroke of the
ventricular pressure pulse which
represents maximum rate of
pressure change
▪ an index of the ability of the
ventricle to generate pressure
during the isovolumic contraction
phase.
▪ occurs just before the opening of
the aortic valve
 Hyperdynamic Heart

Maximum dP/dT
- maximal rate of
change in pressure
with time.

Hypodynamic Heart
 Indices of Cardiac Contractility
▪ Ejection Fraction
▪ ratio of the stroke volume to the end
diastolic volume
▪ the percent of end diastolic volume that
is ejected per beat.
▪ it is about 65%
SV
EF = -----------
EDV
 Heterometric Regulation

▪ Frank Starling’s Law

▪ ability of the heart to
control the strength of
its contraction because
of changes in muscle
fiber length.
BOWDITCH PHENOMENON
▪ (Treppe or staircase phenomenon)
▪ increasing the heart rate into the tachycardia
range results in greater contractility.
▪ positive inotropic
effect.
▪ due to an increase in intracellular calcium.

POST EXTRA-SYSTOLIC POTENTIATION

▪ premature beat or extrasystole is followed by
a stronger beat.
▪ perceived by the person after a "skipped" beat.
▪ attributed to an increase in available intracellular
calcium following the extrasystole.
 BLOOD VESSELS
PULMONARY CIRCULATION

ARTERIES
VEINS

CAPILLARIES

SYSTEMIC CIRCULATION
CAPILLARIES
❖ endothelial cells, basement
membrane
❖ (-) smooth muscle and (-)
elastic tissue
❖ tight junctions, fenestrations
(pores), intercellular cleft and
and pericytes
❖ Total area exceeds 6300 m2 and
1 µm thick
CONTINUOUS CAPILLARIES

FENESTRATED CAPILLARIES

SINUSOIDAL CAPILLARIES

TYPES OF CAPILLARIES
 VEINS
❖ Transport blood
under low pressure.
❖ 8x more distensible
than arteries
❖ transport blood
towards the heart
❖ carry deoxygenated
blood.
Structural and Functional Differences
■ Lumen diameter - V>A>C
■ Wall thickness - A>V>C
■ Blood distribution - V>A>C
■ Total Cross Sectional - C>V>A
■ Blood flow velocity - A>V>C
■ Pressure - A>C>V
■ Resistance - A>C>V
Microcirculation
❖ Purposeful function
❖ transport of nutrients
and oxygen to the
tissues and removal
of waste products and
carbon dioxide from
the tissues
THP
FILTRATION
Subatmospheric = Kf (Factors
or negative Pc – Pif) - (∏
that p - TCOP
affect ∏if)
❖ subcutaneous tissue = Kf (Pc + ∏if) – (Pif + ∏ p)
(8mmHg)
Positive = Kf ❖X protiens
NFP in the
❖ kidney, liver and brain interstitium
❖ other solutes in the
Factors that affect THP interstitium
Factors
❖ solute in thethat affect Kf
interstitium
❖ capillary membrane
PCOP permeability Factors that affect CHP
❖ 28❖mmHgtotal surface area for❖ arterial
35 mmHg
blood pressure
25 mmHg 13 mmHg

❖ 19 mmHg diffusion
(proteins) 9 ❖ arteriolar resistance
mmHg (Donnan Effect) ❖ venular resistance
❖ venous pressure
Factors that affect PCOP
❖ proteins in the plasma
(80% albumin)
Arteriolar end ( Filtration) Venular end ( Reabsorption )

CHP 35 mmHg CHP 15 mmHg

TCOP 8 mmHg TCOP 8 mmHg
------------- -------------
TFP 43 mmHg TFP 23 mmHg

THP 1 mmHg THP 1mmHg

PCOP 25 mmHg PCOP 25 mmHg
-------------- -------------
TRP 26 mmHg TRP 26 mmHg

Total filtration pressure > Total reabsorption pressure

ARTERIOLAR END

Total reabsorption pressure > Total filtration pressure

VENULAR END
BLOOD PRESSURE
■ force exerted by the
blood per unit area of
the vessel wall
(pressure is exerted
equally in all
directions).
Blood Pressure in the Various Parts
of the Systemic Circulation
❖ Mean Blood Pressure
❖ average pressure in any segment of the

cardiovascular system during cardiac cycle.

❖ Arterial Blood Pressure

❖ blood pressure in the arterial side of the vascular

system conveniently written as systolic pressure

over diastolic pressure ( N.V. 100 -130 / 70 - 90
mmHg )
Arterial Blood Pressure
❖ Systolic pressure
❖ highest pressure attained in the aorta as a result of the
ejection of blood by the ventricle.
(N.V. 100 - 120 mmHg )

❖ Diastolic pressure
❖ is the lowest pressure which the gradient of fall reaches
during the resting or diastolic phase of the heart.
( 70 - 80 mmHg )
Pulse Pressure
■ is the difference between the systolic and
diastolic pressure. (SP – DP = 40 mmHg)
■ factors that affect pulse pressure (SV/C)
■ Stroke volume
■ Compliance of arterial tree
Mean Arterial Blood Pressure
➢ represents the average pressure attained in
the arterial system during the cardiac cycle.

MAP = Diastolic Pressure + 1/3 pulse pressure

Diastolic Pressure + ( Systolic – Diastolic pressure )

MAP = -----------------------------------------
3
ABP = CO X TPR

SV X HR

EDV - ESV
BLOOD FLOW
POISEUILLE’S EQUATION
Δ P . r4
F α -----------------
η. L
where,
F = flow
ΔP = pressure difference between
two ends of the vessel
η = viscosity
r4 = radius
L = length of the tube
Since flow (F) is equal to pressure
difference (ΔP) divided by resistance (R)

η. L
R α ------------
r4
FLOW, VELOCITY AND AREA
F
F = V. A or V = ------

where;
F = flow
V = mean velocity
A = cross-sectional area of the blood vessel
BERNOULLI’S PRINCIPLE
Laminar vs. Turbulent Flow
■ Laminar flow (Streamline flow)
■ silent flow
■ characterized by concentric layer of blood moving in
parallel down the length of a blood vessel.
■ Turbulent flow
■ flow that that creates sound
■ probability is also related to the diameter of the
vessel and viscosity of the blood
■ can be expressed by
 p.D .V
Re = ----------------
η
where,
Re = Reynolds number
p = density of the fluid
D = diameter of the tube
V = velocity of flow
η = viscosity of the fluid
LAW OF LAPLACE

T = Pr
Shear Stress and Shear rate
■ Shear Stress
■ Force created by flowing blood on the
endothelium that is parallel to the long axis of
the vessel
■ Equal to viscosity X shear rate
■ Shear rate
■ Rate at which axial velocity from the vessel
wall towards the lumen
Resistance in Series vs Resistance in Parallel
 Systemic regulation of circulation
Question
and Arterial Blood Pressure
When! the chambers
Rapid of the heart are dilated, a
Control
greater tension must be developed in the
myocardium to produce any given pressure. Which
Intermediate
of the! following Control
explains this condition?
A. Reynolds number
B. Ohm’s law
! Long Term Control
C. Poiseuille equation
D. Laplace law
 renal

11 cm – long
6 cm – wide
3 cm - thick

115 – 170 g
 Renal artery
Renal vein

Segmental artery
Segmental vein

Interlobar artery Interlobar vein

Arcuate artery Arcuate vein

20 - 25% - CO (0.5% TBW)
(1200 – 1250 ml/min
Interlobular artery Interlobular vein

Glomerular Efferent Peritubular

Afferent arteriole capillaries capillaries Venule
arteriole
60 mmHg 18 mmHg
 Basic unit of renal
structure and
function

1.2 million each kidney

40 y/o - ↓ 10 % every
10 years
Glomerular capillaries

Peritubular capillaries
 Basement
membrane

1. Lamina densa - central dense layer

2. Lamina rara interna and externa - thinner and more
electroluscent layer
 Nephrotic Syndrome
■ Characterized by an
increase in permeability of
glomerular membrane to
proteins and by loss of
normal podocyte structure,
including effacement of the
podocyte processes.
■ Mutations of the genes that
encode slit diaphragm
proteins.
 Alport’s Syndrome
■ caused by a defect in Type IV collagen.
■ due to mutations of COL4A5 gene (85% x –
linked and mutations in Type IV collagen (15%).
■ irregular thickness of basement membrane (not
effective as filtration barrier)
■ manifestations
■ hematuria

■ progressive glomerulonephritis
Primary Cilium
■ single non motile cilium found in the
apical membrane
■ functions
■ serves as mechanosensors
■ serves as chemosensors
■ initiate calcium dependent signalling
pathway (cell function, proliferation,
differentiation and apoptosis)
Polycystin 1 (PKD1) and 2 (PKD2)
■ are expressed in the membrane of
primary cilia
■ mediates entry of calcium into the cell
■ cell function
■ cell proliferation
■ cell differentiation
■ programmed cell death
Polycystic Kidney Disease (PKD)
■ genetic disease caused primarily by
mutations in PKD1 (85 to 90%) and PKD2
(10 to 15%).
■ manifested by enlargement of the kidney
due to formation of hundreds to
thousands renal cysts.
LACIS CELLS

MACULA DENSA

JG CELLS
Clearance Principle
EXCRETION RATE = FILTRATION RATE - REABSORPTION
RATE + SECRETION RATE
 Determinants of GFR
GFR = Kf X Net Filtration Pressure

Kf = glomerular capillaries filtration coefficient

(capillary permeability and capillary surface area)
Net Filtration Pressure
➢ represents the sum of the hydrostatic and colloid osmotic

forces that either favor or oppose filtration across the

glomerular capillaries.
 TOTAL REABSORPTION PRESSURE
TOTAL FILTRATION PRESSURE

PCOP = 32 mmHg

THP = 18 mmHg

TCOP = 0 mmHg

gCHP = 60 mmHg
 FACTORS AFFECTING GFR

CHANGES IN RENAL BLOOD FLOW

CHANGES IN gCHP
Changes in systemic blood pressure
Afferent arteriolar constriction
Efferent arteriolar constriction

CHANGES IN THP (Pressure in Bowman’s Capsule)

Ureter obstruction
Edema of kidney inside the tight renal capsule

CHANGES IN PCOP (CHANGES IN CONCENTRATION OF PLASMA PROTEINS)

Dehydration
Hypoproteinemia

CHANGES IN KF
Changes in glomerular capillary permeability
Changes in effective filtration surface area
 Question
Kidney function is initially assessed in clinical
setting by;
A. measuring the GFR
B. measuring plasma creatinine concentration
C. measuring the renal blood flow
D. measuring plasma inulin clearance
Two Mechanisms Responsible for the
Autoregulation of RBF and GFR
■ Mechanism that responds to changes in
arterial blood pressure (Pressure- Sensitive
Mechanism)
■ Myogenic mechanism
■ Mechanism that responds to changes in tha
NaCl composition of tubular fluid (NaCl –
dependent Mechanism)
■ Tubulofeedback Mechanism (Juxtaglomerular
Apparatus)
RENAL BLOOD FLOW
Nervous mechanism
■ Sympathetic Nervous System
■ mild and moderate sympathetic activation

■ little effect on both the RBF and GFR

■ strong activation

■ decreases RBF and GFR

 Hormones and Autocoids
■ Norepinephrine and Epinephrine
■ Endothelin
■ Adenosine
■ Angiotensin II
■ Nitric oxide
■ Prostaglnadin
■ Dopamine
■ Acetylcholine
■ Bradykinin
 FLUIDS AND ELECTROLYTES: 

Body Water Content

The “average” man

70 kg contains about 60%
water by weight.

175 cm In many clinical

situations, we will not be
dealing with “average”
people.
"Juan"
FLUIDS AND ELECTROLYTES
Here is a useful mnemonic:
the 60:40:20:15:5 rule. Memorize it.

■ Total Body Water 60% of body weight

■ Intracellular fluid 40% of body weight
■ Extracellular fluid 20% of body weight
■ Interstitial Water 15% of body weight
■ Plasma 5% of body weight
FLUID OSMOLARITY
ECF - Extracellular Fluid (synovial fluid, CSF, etc)
(Interstitial and intravascular fluid)

ECF Na+ - major determinant of ECF

osmolarity

ICF Plasma Osmolarity

= 2 (Plasma [Na+ ])
= 2 (145) = 290 mOsm/L

ICF - Intracellular Fluid

 In clinical situations, a more accurate estimate of
plasma osmolarity is obtained by the considering
the osmoles contributed by urea and glucose

[Glucose] [Urea]
Plasma Osmolarity = 2 ((Plasma [Na+ ]) + ----------- + -------
18 2.8

The glucose and urea concentrations are expressed in units of

mg/dL(dividing by 18 for glucose and 2.8 for urea* allows
conversion from the units of mg/dL to mmol/L and thus to
mOsm/kg H2O). This estimation is useful in patients with
diabetes mellitus and chronic renal failure.
 Compensatory
FLUID ECF FLUID ICF
Mechanism
INFLUX SHIFT VOLUME
VOLUME Osmolarity Osmolarity

ISOTONIC same
↑
0.9 % NaCl same none same same none
or NSS
5% Dextrose
HYPOTONIC
< 0.9% NaCl
<5% dextrose
H2 O loading ↑ ↓ → ↑ ↓ ↓ Osmolarity
(Hyposmotic
Overhydration)
↓ ADH
Excess ADH
Bronchogenic Ca

HYPERTONIC
> 0.9% NaCl
> 5% dextrose
(Hyperosmotic ↑ ↑ ← ↓ ↑ ↑ Osmolarity
Ovehydration)
Cushing’s Dse
↑ ADH
Primary
Aldosteronis
 Compensatory
FLUID ECF FLUID ICF
Mechanism
EFFLUX SHIFT VOLUME
VOLUME Osmolarity Osmolarity

ISOTONIC same
0.9 % NaCl ↓ same none same same none
5% Dextrose
(Burns)
HYPOTONIC
< 0.9% NaCl
<5% dextrose ↓ ↑ ← ↓ ↑ ↑ Osmolarity
(Hyperosmotic
Dehydration)
↑ ADH
Diabetes Insipidus
Excessive sweating

HYPERTONIC
> 0.9% NaCl
> 5% dextrose
(Hypoosmotic ↓ ↓ → ↑ ↓ ↓ Osmolarity
dehydration)
Adrenal ↓ ADH
Insufficiency
Overuse of
diuretics
SIADH
 SUMMARY
H2O DEPRIVATION EXCESS WATER

DEHYDRATION OVERHYDRATION

ANTIDIURETIC STATE DIURETIC STATE

! ECF TONICITY " ECF TONICITY

(+) OSMORECEPTORS (-) OSMORECEPTORS

! ADH SECRETION/RELEASE " ADH SECRETION/RELEASE

! PERMEABILITY OF DCT/CD TO WATER " PERMEABILITY OF DCT/CD TO WATER

! H2O REABSORPTION IN DCT/CD " H2O REABSORPTION IN DCT/CD

" URINE VOLUME /! URINE ! URINE VOLUME /" URINE

TONICITY TONICITY
CONCENTRATED URINE DILUTED URINE
 Free Water Clearance
■ Positive Free Water Clearance
■ Excess water is excreted by the kidney
■ Urine osmolarity is lesser than plasma osmolarity
■ Water excretion
■ Negative Free Water Clearance
■ Excess solutes are removed from the body
■ Urine osmlarity is greater than plasma osmolarity
■ Water conservation
 CLINICAL IMPLICATION

DIABETES INSIPIDUS
Central Diabetes Insipidus
■ a.k.a. pituitary diabetes insipidus
■ inadequate release of ADH
(ADH deficiency)
■ ADH level is low
■ can be inherited and commonly
caused by brain neoplasms
(30%), head trauma (30%),
idiopathic (30%) infection,
vascular lesions and others
■ treatment is administration of
exogenous ADH
■ polyuria and polydipsia
Nephrogenic Diabetes Insipidus
■ diabetes insipidus with primary
defect in the kidney
■ inability of the kidney to respond to
ADH
■ ADH level is normal or high
■ congenital defect in V2 receptor (X-
linked, 90%) or non functional
AQP2 (10%), drugs (lithium),
ureteral obstruction, low protein diet
and hypercalcemia
■ Polyuria and polydipsia
SIADH
■ Syndrome of Inappropriate Hypersecretion of Antidiuretic
Hormone
■ high plasma level of ADH above what would be expected on
the basis of body fluid osmolality and blood volume and
pressure.
■ water is retained hence produce concentrated urine
■ result to body fluid hypoosmolality (dilutional
hyponatremia)
■ can be due to brain neoplasm and infection, drugs, cerebral
disease (cerebral salt wasting) and pulmonary disease
(pulmonary salt wasting)
 DEFINITION
■ ACID ■ BASE (ALKALI)
■ a substance that can ■ a substance that can
donate or release combine with or accept
hydrogen ion (H+). hydrogen ion (H+) .
■ hydrogen donor ■ hydrogen acceptor
■ examples ■ examples
■ HCl (strong acid) ■ OH- (strong base)
■ H2CO3 ■ HCO3-
■ H2PO4 ■ HPO4 =
■ H3PO4 ■ H2 PO4-
■ Proteins (hemoglobin)
 Hydrogen Ion (H+)
■ a single free proton released from a
hydrogen atom.
■ released in large amount in solutions from
strong acids (HCl).
■ removed rapidly from the solutions by
strong bases (OH-).
■ its concentration influenced the activities of
almost all cells in the body
 pH units
■ express the hydrogen ion concentration on
a logarithm scale. (40neq/L)
■ related to the actual hydrogen ion
concentration.
■ formula:
1
pH = ----- = - log (H+ )
(H+ )
pH = - log (0.00000004)
pH = 7.4
 [H+] nmol/L

42 41 40 39 38

7.38 7.39 7.40 7.41 7.42

pH units
In the events of everyday life, the variation of
ECF pH is very narrow.
One nmol of H+/L = 0.01 pH unit
 [H+] nmol/L
125 20

6.9 7.7
pH units
In abnormal situations, much wider changes may
be seen. In practice, a pH of 6.9 or 7.7 will only
be seen in profound pathological situations.
 ■ a diet containing both meat
H+ and vegetables results in net
acid production.

■ the balance of acid-forming

and acid-consuming
metabolic reactions results
in net production of about
0.7 – 1.0 meq H+/kg body
(50-100 mEq/day weight/
day) in an adult who eats a
mixed diet.
 Sources of H+ ions in the body
■ Metabolism of foodstuffs – produces about 300 liters of
CO2 (15 to 20 moles) ---- volatile acids
■ Incomplete metabolism of CHO and fats – produces
nonvolatile acids, eg. lactic acid from glucose; acetoacetic
and β- hydroxybutyric acid from fatty acid oxidation -----
non -volatile acids
■ Oxidation of proteins and amino acids – produces strong
acids, eg. H2SO4 (cysteine and methionine), HCl (lysine,
arginine and histidine), and H3PO4 –--- non -volatile acids
 Sources of HCO3- ions in the
body
■ hydration of CO2 (CO2 + H2O) — HCO3- + H+
■ metabolism of aspartate anf glutamate
■ metabolism of citrate

■ Effect - net production of acid

■ diet - acid > alkali
■ metabolism - acid > alkali
■ GIT - loss of HCO3-
Acids are continuously
produce in the body and
threaten the normal pH of
body fluids.
Carbonic acid
(H2CO3)
Noncarbonic acids
nonvolatile or
fixed acids
 HENDERSON – HASSELBALCH EQUATION

HCO3 - kidney
pH = --------------------
(0.03 X CO2) - lungs

Medical Physiology by Guyton and Hall

Eleventh Edition
 Acidification of the Urine
acidosis alkalosis
↑ ■ Bicarbonate reabsorption ↓

↑ ■ Production of new bicarbonate ↓

↑ ■ Hydrogen secretion ↓

↑ ■ Acidifying urinary buffers ↓

↑ ■ Formation of NH3 to NH4 ↓
 FATES OF SECRETED H+

1. 90% TITRATES FILTERED BICARBONATE

IN A RECLAMATION PROCESS (H2CO3 ----- CO2 + H2O)

2. 1% IS BUFFERED BY NH3 TO FORM NH4+

3. 1 % IS BUFFERED BY OTHER TUBULAR BUFFERS

MOSTLY HPO4= TO FORM TITRATABLE ACIDITY

4. A VERY MINUTE AMOUNT OF H+ REMAINS FREE

IN THE FINAL URINE
Variation in pH of the tubular fluid
along the nephron

Schmidt, Human Physiology,1989

Acid – Base Disorder

HCO3- (kidneys)
pH = --------------
PCO2 (lungs)
 Metabolic Acidosis
■ Characterized by decreased ECF HCO3 and
pH or any type of acidosis besides those
caused by excess PCO2 .

↓ HCO3-
↓ pH = --------------
↓ PCO2
■ ↓ 1.2 mmHg in PCO2 for every 1 meq/L ↓ in HCO3-
 Metabolic Acidosis
■ causes
■ kidney diseases (chronic renal failure, renal
tubular acidosis and Fanconi’s syndrome)
■ Metabolic disorders (Diabetes mellitus)
■ Gastrointestinal disorders (diarrhea, vomiting of
intestinal content and ingestion of acids ex.
acetylsalicylic acid and methyl alcohol)]
■ loss of non volatile base or addition of non volatile acid
 Metabolic Alkalosis
■ Characterized by increased ECF HCO3 and
pH or any type of alkalosis besides those
caused by deficient PCO2 .

↑ HCO3-
↑ pH = --------------
↑ PCO2
■ ↑ 0.7 mmHg in PCO2 for every 1 meq/L ↑ in HCO3-
 Metabolic Alkalosis
■ causes
■ Hemorrhage
■ ECF volume contraction
■ Excess aldosterone
■ loss of hydrogen ions
■ Gastrointestinal disorders (vomiting of gastric
content and ingestion of alkaline drugs like
antacid)
■ loss of non volatile acid or addition of non volatile base.
 Respiratory Acidosis
■ Characterized by an elevated CO2 and reduced
ECF pH.

↑ HCO3-
↓ pH = --------------
↑ PCO2
■ ↑ 1 meq/L in HCO3- for every ↑ 10 mmHg in PCO2, and a ↓ in pH
by 0.08 (acute)
■ ↑ 3.5 meq/L in HCO3- for every ↑ 10 mmHg in PCO2, ↓ in pH by
0.03 (chronic)
 Respiratory Acidosis
■ causes
■ Drug – Induced Respiratory Depression
■ decreased gas exchange (↓ ventilation)
■ Cardiovascular and Pulmonary Diseases
■ impaired gas diffusion
 Respiratory Alkalosis
■ Characterized by an reduced CO2 and elevated
ECF pH.

↓ HCO3-
↑ pH = --------------
↓ PCO2
■ ↓ 2 meq/L in HCO3- for every ↓ 10 mmHg in PCO2, ↑ in pH by 0.08
(acute)
■ ↓ 5 meq/L in HCO3- for every ↓ 10 mmHg in PCO2, ↑ in pH by 0.03
(chronic)
 Respiratory Alkalosis
■ causes
■ Respiratory Center Stimulation (drug-
induced, ascent to high altitude, anxiety, pain
and fear)
■ increased gas exchange (↑ ventilation)
■ Psychoneurosis
■ SYNTHESIS OF ERYTHROPOPOIETIN

■ ACTIVATION OF VITAMIN D

■ SYNTHESIS OF RENIN