High Yield Topics for

Physiology

Physicians’ Licensure Examination

Review
May 2010
How should I study
for the Physiology aspect
of the Physicians’ Licensure Exam (PLE)?
 Study Smart
Study Scientific
Study High Yield
Some General Tips for studying for the Boards:

1. Set realistic study goals - know your effective study

behavior.
2. Mastery of all topics is IMPOSSIBLE - learning everything
should not be your goal.
3. Be selective with the books and notes you use.
4. Go through the different subjects more than once.
Some suggested effective study strategies:

1. ACTIVATE
• Avoid just skimming or highlighting.
• Take an overview, reorganize the information, jot down
notes, draw diagrams, make charts.
1. INTEGRATE
• Think how the topic relates to others.
1. VARIEGATE
• Keep your mind engaged, let it wander in relation to the
topic.
• Use flashcards, pictures, charts, graphs, outlines.
1. EVALUATE
• Self-test, re-draw diagrams, reviewers
Tips for studying Physiology for the USMLE:

1. As a general principle, the physiology underlying

mechanisms of action of major clinical drugs is important
to remember.

2. Hormone production, regulation, receptors, and effects are

worth learning in detail.

3. The renin-angiotensin-aldosterone axis and the effects of

aldosterone deficiency and excess in particular are high
yield.
Tips for studying Physiology for the USMLE:

4. Basic equations and other formulas such as the Fick

equation and renal clearance appear consistently over the
years.

5. The cardiac action potential and cardiac cycle are high

yield.
Tips for studying Physiology for the PLE:
Tips for studying Physiology for the PLE:

Study Smart
Study Scientific
Study High Yield
The Physiology exam of the PLE:

Types of questions:

1. RECALL

2. COMPREHENSION

3. ANALYSIS
The Physiology exam of the PLE:
100%
90%
80%
70%
%age 60% Analy
50% Compr
40% Recall
30%
20%
10%
0%
1995 1996 1997 1998 2000 2001 2002

Exam Year
 The previous exam listed
questions which appeared twice
or more than twice in the past
seven years
High Yield Topics in Physiology
Some HIGH YIELD topics in Physiology:
A. Cardiovascular

Cardiac Output

cardiac output = (stroke volume) x (heart rate)

(how do certain events affect cardiac output?

For example, does exercise increase CO primarily
as a result of increased stroke volume or increased
heart rate?)
Some HIGH YIELD topics in Physiology:
A. Cardiovascular
Cardiac Output Variables

Stroke Volume is affected by

Contractility, Afterload, Preload

Contractility (and SV) increased with: 1. Catecholamines

2. Inc. extracellular Ca
3. Dec. extracellular Na
4. Digitalis

Contractility (and SV) decreased with: 1. Beta blockade

2. Heart failure
3. Acidosis
4. Hypoxia/hypercapnea
Some HIGH YIELD topics in Physiology:
A. Cardiovascular
Preload and afterload

Preload = ventricular EDV

Afterload = total peripheral resistance

Stroke volume increases when preload increases or

afterload decreases
Some HIGH YIELD topics in Physiology:
A. Cardiovascular
Ejection Fraction

Ejection Fraction = enddiastolic volume - endsystolic volume

enddiastolic volume

ejection fraction is an index of ventricular function

Some HIGH YIELD topics in Physiology:
A. Cardiovascular
Resistance, pressure, flow

Resistance = driving pressure (or ∆P)

Flow

Resistance factors

Poiseuille’s Law: resistance is directly proportional to:

-viscosity of the fluid and
-length of the tube
resistance is inversely proportional to:
-(radius)4
Some HIGH YIELD topics in Physiology:
A. Cardiovascular
Capillary fluid exchange

Four forces (Starling Forces) determine fluid movement

through capillary membranes

Pc = capillary pressure (hydrostatic pressure)

Pi = interstitial pressure
πc = plasma oncotic pressure
πi = interstitial oncotic pressure

Net Pressure = Pnet = (Pc - Pi) - (πc - πi)

Some HIGH YIELD topics in Physiology:
A. Cardiovascular
Cardiac Action Potential (ventricular)

Phase 0 - rapid depolarization, (at -90mV)

- opening of voltage gated Na channels
- influx of Na
Phase 1 - partial repolarization (at +20mV)
- small increase in K permeability
Phase 2 - plateau (unique to cardiac action potential)
- slow Ca channel
- slow Ca influx
Phase 3 - rapid repolarization
- increased K permeability
Phase 4 - diastolic depolarization
- decreased baseline K permeability
Some HIGH YIELD topics in Physiology:
A. Cardiovascular
Cardiac Cycle (visualize the pressure-volume loop)
Phases: 1. Isovolumic contraction
- between mitral closure and aortic opening
2. Systolic ejection
- between aortic opening and closure
3. Isovolumic relaxation
- between aortic closure and mitral opening
4. Rapid filling
- follows mitral opening
5. Slow filling
- just before mitral closure
Some HIGH YIELD topics in Physiology:
A. Cardiovascular
Heart Sounds

…S4…S1…..S2…S3….

S1 - mitral and tricuspid valve closure

S2 - aortic and pulmonary valve closure
S3 - end of rapid ventricular filling
S4 - high atrial pressure/stiff ventricle
Some HIGH YIELD topics in Physiology:
A. Cardiovascular
Electrocardiogram

P wave - atrial depolarization

PR interval - conduction delay through AV node
QRS comples - ventricular depolarization
QT interval - mechanical contraction of ventricles
T wave - ventricular repolarization

atrial repolarization? It is masked by QRS complex

Secondary or tertiary Avblock shows many P waves
for each QRS
Some HIGH YIELD topics in Physiology:
A. Cardiovascular
Cardiovascular regulation

Arterial baroreceptors
1. Aortic arch transmits via vagus nerve to medulla
2. Carotid sinus transmits via glossopharyngeal n.

Increased arterial pressure leads to increased afferent

baroreceptor firing, which leads to an increase in
efferent parasympathetic stimulation, and decrease in
sympathetic firing.
Some HIGH YIELD topics in Physiology:
A. Cardiovascular
Cardiovascular regulation

Chemoreceptors:

Peripheral: 1. Aortic bodies: respond to dec PO2, inc PCO2

2. Carotid bodies: respond to dec PO2, inc PCO2,
dec pH
Central: Respond to changes in pH and PCO2 of brain
interstitial fluid, which in turn are influenced
by arterial CO2. Does not directly respond to
PO2.
Some HIGH YIELD topics in Physiology:
B. Respiratory
Response to high altitude

1. Acute increase in ventilation by 65%

2. Chronic increase in ventilation by 3-7%
3. Increase hematocrit (polycythemia) and hemoglobin conc
4. Increased 2,3 DPG (Hb lets go of O2 more readily)
5. Cellular changes (increased mitochondria)
Some HIGH YIELD topics in Physiology:
B. Respiratory
Important lung products:

1. Surfactant
2. Prostaglandins
3. Histamine
4. Angiotensin converting enzyme
5. Kallikrein
Some HIGH YIELD topics in Physiology:
B. Respiratory
Particle size and lung entrapment

Diameter of: >4-6um - trapped in nose, trachea, bronchial

tree
1-5 um - trapped in small bronchioles
0.5-1um - trapped in fluid on walls of alveoli
<0.5 um - suspended in air

Particles trapped are pushed out by cilia.

Kartagener’s syndrome = immotile cilia; the bacteria and
particles are not pushed out
Some HIGH YIELD topics in Physiology:
B. Respiratory
Lung Volumes

1. Residual volume - air left after maximal expiration

2. Expiratory Reserve Volume - air that can still breath out
after normal expiration
3. Tidal volume - air that moves into lung with each breath
4. Inspiratory Reserve Volume - air in excess of tidal volume
that moves into lung on maximum inspiration
5. Vital Capacity = TV + IRV + ERV
6. Functional Reserve Capacity = RV + ERV
7. Inspiratory Capacity = IRV + TV
Some HIGH YIELD topics in Physiology:
B. Respiratory
Oxygen dissociation curve

Hemoglobin releases oxygen more easily (shifts to the

right) when:
1. Inc. acidity
2. Inc. 2,3 DPG
3. Inc. temperature
4. PCO2

“an acidotic, hot, hypercapnic person with lots of 2,3 DPG in

his blood has oxygen dissociating from hemoglobin most
quickly.”
Some HIGH YIELD topics in Physiology:
C. Gastrointestinal
Carbohydrate digestion
1) Salivary amylase: starts digestion by hydrolyzing alpha
1,4 linkages to give maltose, maltotriose, and dextrans
2) Pancreatic amylase: highest concentration in duodenal
lumen, hydrolyzes starch to oligosaccharides, maltose, and
maltotriose
3) Oligosaccharide hydrolases: at brush border of intestines,
is the rate limiting step in carbohydrate digestion, yields
monosaccharides
Some HIGH YIELD topics in Physiology:
C. Gastrointestinal
Salivary secretion

Source Parotid, submaxillary, and sublingual glands

Function Maintains moistness of mouth for speech

Lubricates food for tasting ans swallowing
a-amylase begins starch digestion
Neutralizes oral bacterial acids, for dental health

Regulation Stimulated by acid in mouth, chewing, neural

afferents in pharynx, mouth, and olfactory area
Some HIGH YIELD topics in Physiology:
C. Gastrointestinal
Glucose absorption
1) Occurs at duodenum and proximal jejunum
2) Transported across cell membrane by carrier-mediated
process
3) Sodium-glucose coupled absorption driven by intracellular
sodium concentration
Some HIGH YIELD topics in Physiology:
C. Gastrointestinal
Stomach
Secretions
Purpose Source
Mucus lubricant, protects from H+ Mucous cell
Intr Factor B12 absorptn Parietal cell
H+ kills bacteria, converts Parietal cell
pepsinogen
Pepsinogen breaks down to pepsin Chief cell
Gastrin Stimulates acid secretion G cell
Some HIGH YIELD topics in Physiology:
C. Gastrointestinal
Gastric Acid

Source Parietal cells in stomach

Function Lowers pH to optimal range for pepsin function

Sterilizes chyme

Regulation Stimulated by histamine, Ach, gastrin, amino acids

Inhibited by prostaglandins
Some HIGH YIELD topics in Physiology:
C. Gastrointestinal
Parietal cell control

Parietal cell has four receptors:

Ach - blocked by pirenzipine
Gastrin
Histamine - blocked by cimetidine, ranitidine
Prostaglandin - stimulated by misoprostol

Common pathway for H+ secretion is ATPase (proton) pump,

which is blocked by omeprazole
Some HIGH YIELD topics in Physiology:
C. Gastrointestinal
Gastrin

Source -Endocrine cells of antrum and duodenum

Function-Stimulates H+ secretion by parietal cells

-Weakly stimulates pancreatic enzymes
-Increases Lower Esophageal Sphnctr tone
-Promotes contraction of circular muscles
-Promotes stomach emptying
-Relaxes ileo-cecal sphincter

Regulation -Stimulated by food, digestion, amino acids,

vagal input, and alcohol.
-Inhibited by secretin, stomach pH<1.5
Some HIGH YIELD topics in Physiology:
C. Gastrointestinal
Bicarbonate

Source surface submucosal cells

Function Neutralizes acid, forms an unstirred layer with

mucus on the luminal surface of gastric mucosa
Some HIGH YIELD topics in Physiology:
C. Gastrointestinal
Intrinsic factor

• Vitamin B12 binding protein required for its

absorption in the terminal ileum of the small
intestine.
• Secreted by parietal cells. Autoimmune
destruction of these parietal cells leads to
pernicious anemia.
Some HIGH YIELD topics in Physiology:
C. Gastrointestinal
Bilirubin: - Product of heme metabolism, actively taken
up by hepatocytes.
- Conjugated form is water soluble.

Bile: - contains water, phospholipids, bile acids,

cholesterol, bilirubin

Gallbladder contraction: stim by Ach, CCK, secretin, gastrin

Some HIGH YIELD topics in Physiology:
C. Gastrointestinal
Anatomy of pancreatic secretion

Secretory acini synthesize and secrete zymogens,

stimulated by insulin, and inhibited by glucagon.

Pancreatic ducts secrete mucus and alkaline fluid.

 Some HIGH YIELD topics in Physiology:
C. Gastrointestinal
Pancreatic enzymes
• alpha amylase - starch digestion, secreted in active
form
• lipase, - fat digestion
phospholipase A
colipase
• proteases - protein digestion, secreted as pro-enzymes
trypsin
chymotrypsin
elastase
carboxypeptidase
Some HIGH YIELD topics in Physiology:
C. Gastrointestinal
Cholecystokinin

Source -Endocrine cells of duodenal and jejunal mucosa

Function-Increases GB contraction and relaxation of

sphincter of Oddi
-Stimulates pancreatic secretion enzymes and
bicarbonate
-Increases intestinal peristalsis
-Slows gastric emptying
Regulation - Stimulated by digestion products, amino acids
(esp tryptophan)
Some HIGH YIELD topics in Physiology:
C. Gastrointestinal
Secretin

Source -Endocrine cells of small intestine

Function Nature’s antacid:

-Increases pancreatic bicarbonate secretion
-Contracts pyloric sphincter and slows emptying time of
stomach
-Increases bile secretion
-Augments CCK-induced pancreatic secretion of
digestive enzymes
-Reduces acid secretion in stomach

Regulation - Stimulated by acidification of duodenal mucosa,

digestive products of fat and protein
Some HIGH YIELD topics in Physiology:
C. Gastrointestinal
Somatostatin

Source -Pancreatic D cells, gastric antrum, intestinal endocrine

cells

Function Very inhibitory hormone: (think anti-growth hormone

effects, i.e. decreases digestion and inhibits absorption of
substances needed for growth)
-Inhibits: GB contraction, gastric acid and pepsinogen
secretion, pancreatic and small intestinal fluid
secretion, Ach release from myenteric plexi

Regulation - Stimulated by gastric acid in lumen

Some HIGH YIELD topics in Physiology:
D. Renal
Some formulas:

• Filtration Fraction: FF = GFR/RPF

• Renal clearance: Cx = U x V/Px = volume of plasma
from which the
substance is cleared
completely per unit
time
If Cx < GFR, then x is reabsorbed
If Cx > GFR, then x is secreted
If Cx = GFR, then x is in equilibrium
Some HIGH YIELD topics in Physiology:
D. Renal
Some formulas:

• Glomerular Filtration Rate

GFR = Uinulin X V / Pinulin = Cinulin

*inulinisfreelyfiltered, neitherabsorbedorsecreted

• Effective renal plasma flow

ERPF = UPAH X V / PPAH = CPAH = RBF (1-Hct)

• Renal blood flow

RBF = ERPF x 1 / (1-Hct)
Some HIGH YIELD topics in Physiology:
D. Renal
Glucose clearance

- glucose at normal level is completely reabsorbed,

(99% at proximal tubule, 1% in collecting ducts)
- mechanism is saturable; renal threshold is 200mg/dl of
arterial plasma
Some HIGH YIELD topics in Physiology:
D. Renal
Amino Acids clearance

- Reabsorption by three distinct carrier systems, with

competitive inhibition within each group
- Active transport occurs at proximal tubule and is
saturable.
Some HIGH YIELD topics in Physiology:
D. Renal
Electrolytes clearance

Na - 99% of filtered load is absorbed. Reabsorption is active

throughout most of nephron. No maximal rate of transport.

Cl - Reabsorption is passive, driven by potential and

concentration differences maintained by sodium (except at
thick ascending loop of Henle)
Some HIGH YIELD topics in Physiology:
D. Renal
Renal tubule physiology
Organic acids
And bases, H+

1 K, H
3
Urea, NaCl,
NaHCO3 Na K,
H20, glucose, Na H
Amino acids 2 K
urea
Cl
H20
4
urea Na, Cl
H20
1. Acetazolamide
2. Furosemide
3. Thiazide, aldosterone, spironolactone
4. ADH
Some HIGH YIELD topics in Physiology:
E. Endocrine
Hormone Transport in Blood

• Peptide hormones are hydrophyllic and freely dissolve in

plasma
• Steroid and thyroid hormones are hydrophobic and require
plasma proteins to carry them
• Some plasma binding proteins such as thyroid binding globulin,
bind only specific hormones; others such as albumin,bind
virtually all hormones
• The total hormone pool is predominantly in bound form,
however, only the free form of hormone is biologically active
Some HIGH YIELD topics in Physiology:
E. Endocrine
Anterior Pituitary gland hormones
1) Prolactin
- after pregnancy, stimulates lactose synthesis
- Supresses LH secretion, leading to amenorrhea
2) ACTH
- Stimulates cortisol release from the adrenal cortex
3) GH
- Stimulates the growth of bone, cartilage, and connective tissue.
- Anabolic effect on skeletal and cardiac tissue leading to positive
nitrogen balance.
- Catabolic efect on adipose tissue.
- Diabetogenic efect (anti-insulin effects)
- Stimulates mammary gland development and milk production
4) TSH - stimulates T3 and T4 release from the thyroid
Some HIGH YIELD topics in Physiology:
E. Endocrine
Posterior Pituitary gland hormones (neural hormones)
1) ADH (from supraoptic nucleus)
- Increases permeability of renal collecting ducts to water, leading to
water reabsorption
- Decreases volume and increases osmolality of urine
- Decreases blood flow to renal medulla
- Stimulates release of ACTH from anterior pituitary
- potent vasoconstrictor

2) Oxytocin (from paraventricular nucleus)

- Stimulates uterine contractions during labor
- Stimulates myoepithelial cells of the mammary gland to contract an
dcause milk letdown
Some HIGH YIELD topics in Physiology:
E. Endocrine
Thyroid gland hormones
1) Thyroid Hormone
- Increases basal metabolic rate of most cells in the body and increases
the activity of Na/K ATPase pumps
- Necessary for normal bone growth and maturation, normal brain
maturation, and normal lactation

2) Calcitonin (“calcium to in”)

- Secreted by parafollicular cells (C cells) of thyroid
- Inhibits bone resorption by osteoclasts and osteocytes
- Inhibits gastric motility and gastrin secretion
- Prevents absorption of Ca and PO4 in jejunum
- Stimulates excretion of Ca, Na, and phosphate in the kidney
- Decreases calcitriol synthesis by inhibiting 1α -hydroxylase
- results in hypocalcemia due to inc Ca uptake to bone
Some HIGH YIELD topics in Physiology:
E. Endocrine
Thyroid gland hormones
Important points:
• During thyroid hormone synthesis, follicular cells become columnar
• The thyroid cell actively transports iodide into the cell. ?The iodide
then diffuses into the colloid.
• T4 and T3 are synthesized in colloid by iodination and condensation
of tyrosine molecules bound in peptide linkage to thyroglobulin.
• T3 very significantly and rapidly
increases BMR, but its effect is more transient.
• T4 is weaker, but its effects last longer.
-
hypothalamus
+ TRH
T3 - Ant pituitary
T4
+ TSH
Thyroid
Some HIGH YIELD topics in Physiology:
E. Endocrine
Parathyroid gland hormones
PTH
• Overall osteolytic effect by stimulating osteoclastic and osteocytic
activity while suppressing osteoblastic activity. This release of Ca
and PO4 from bone may cause hypercalcemia.
• Acts together with calcitriol to increase intestinal absorption of Ca and
PO4.
• Stimulates absorption of Ca in the distal nephron, but inhibits Ca
absorption in the proximal tubule.
•
-
Increases calcitriol synthesis by stimulating 1α -hydroxylase activity.
• Increases renal excretion of Na, K, HCO3.

**study calcium regulation,

Vit D metabolism (biochem)
Some HIGH YIELD topics in Physiology:
E. Endocrine
Parathyroid gland hormones
PTH

Source: Chief cells of parathyroid

Function: 1. Inc bone resorption of Ca
2. Inc kidney resorption of Ca
3. Dec kidney resorption of PO4
4. Inc 1,25 vit D production
-
(cholecalciferol)
Regulation: Increases in Ca decrease secretion
**PTH: increases serum Ca,
decreases serum PO4, increases
urine PO4
Some HIGH YIELD topics in Physiology:
E. Endocrine
Vitamin D
Source: Vit D3 from sun exposure in skin.
Vit D2 from plants.
Both converted to 25-D in liver.
1,25-D in kidney

Function: Inc absorption of dietary Ca

Inc absorption of dietary PO4
-
Regulation: Inc PTH causes inc 1,25D conversion
Dec PO4 causes inc 1,25D conversion
1,25D negative feedback

Vit D deficiency: ricketts (kids); osteomalacia (adults)

Some HIGH YIELD topics in Physiology:
E. Endocrine

“salt” Mineralocorticoids
Zona glomerulosa
(aldosterone)
medulla cortex

Zona fasciculata “sugar” Glucocorticoids

(cortisol) -
Zona reticularis “sex” Gonadotropes
(sex steroids)
“stress” Catecholamines
(epinephrine, norepinephrine)
Some HIGH YIELD topics in Physiology:
E. Endocrine
Adrenal Cortex hormones
Aldosterone
• Increases Na reabsorption in the distal convoluted tubule

Cortisol
• Anti-inflammatory effects
• Stress adaptation
• Stimulates gluconeogenesis, blocks uptake of glucose in tissues, and
inhibits glycolytic enzymes -
• Mobilizes fatty acids from adipose tissue to the liver and stimulates
lipolysis
• Increases release of amino acids from skeletal muscle and other
tissues while inhibiting protein synthesis. This leads to a negative
nitrogen balance.
 Some HIGH YIELD topics in Physiology:
E. Endocrine Trauma
Cortisol Feedback Inhibition Emotion
Drive for Circadian rhythm
Adrenal Insufficiency:
+
Primary - reduced adrenal cortex or
metabolic failure of hormone -
- ACTH elevated hypothalamus

Secondary - Hypothalamic/pituitary disease + CRH

or suppression
-
- ACTH decreased Pituitary gland

cortisol + ACTH

Adrenal cortex
Some HIGH YIELD topics in Physiology:
E. Endocrine
Adrenal Medulla hormones
Epinephrine and Norepinephrine
• Sympathetic effects on target organs
• Elevates blood glucose
• Adrenal medulla is the only tissue that can convert NE

Epinephrine Norepinephrine
Receptor predominance b>a a>>b
Total peripheral resistance dec dec
Cardiac Output inc dec
Heart rate inc dec
Blood pressure no change inc
Some HIGH YIELD topics in Physiology:
E. Endocrine
Kidney hormones

• Renin - release stimulated by a drop in serum

Na and a decrease in blood flow to the
kidneys
- converts angiotensin to angiotensin I
• Calcitriol - 1,25-dihydroxy vit D3
- works synergistically with PTH to
increase absorption of Ca and
phosphate in the small intestine

**study renin-angiotensin-aldosterone pathway

 Some HIGH YIELD topics in Physiology:
E. Endocrine
Male spermatogenesis
Products Functions
Sertoli cells androgen binding protein Ensures high levels of
testosterone in seminiferous
tubules
inhibin Inhibits FSH

Leydig cell testosterone Differentiation of male

genitalia
Anabolic effects on protein metab
Gametogenesis maintenance
Libido
Inhibits LH
FSH Stimulates Sertoli cells
Required for gamete maturation LH
Stimulates Leydig cells