Physiology - General

Front 1

Body composition of average young adult male
a. Percent water
b. Percent protein and related substances
c. Percent minerals
d. Percent fat

Back 1

a. Water- 60%
(2\3 intracellular, 1\3 extracellular of this 3\4 interstitial and 1\4 plasma)
(Lower in females and with older age. Fat have low water (hydrophobic), so increasing fat stores equals less water)

b. Protein - 18%

c. Minerals - 7%

d. Fat - 15%

(Ganong)

Front 2

Water physiology
a. How can the total blood volume be calculated when the plasma volume and hematocrit is known
b. Why does dehydration develop more rapidly and is frequently more severe in children

Back 2

a. Total blood volume = plasma volume x (100\(100 - hematocrit))

b. The ECF volume\intracellular fluid volume ratio is larger in infants and children than in adults

(Ganong)

Front 3

Osmolal
a. Osmolal concentration - Definition
b. Is the effect of a 5% glucose solution after the initial phase effect iso-, hypo- or hypertonic
c. Simplified equation for plasma osmolality
d. How does cells counteract swelling from hypotonicity

Back 3

a. Osmolal concentration
I. Measured by the degree to which it depresses the freezing point, with 1 mol of an ideal solution depressing the freezing point 1.86 C
(The freezing point of normal human plasma averages -0.54 C, which corresponds to an osmolal concentration of 290 msom\L)

b. Hypotonic, because the glucose is rapidly metabolized
(Tonicity is used to describe the osmolality of a solution relative to plasma)

c. Plasma osmolality = 2 x [Na] + [Glu] + [Urea]

d. Mechanisms for cells to counteract swelling
1. Swelling activates channels that permit increased efflux of K and Cl, and small organic solutes called organic osmolytes

(Ganong)

Front 4

Donnan effect
a. Donann effect
b. The three effects of the Donnan effect on the distribution of ions in the body

Back 4

a. Donnan effect
I. Explains the distribution of ions to which a membrane is permeable when an ion is present that cant diffuse across the membrane
(Gibbs-Donnan equation - in the presence of a nondiffusible ion, the diffusible ions distribute themselves so that at equilibrium, their concentration ratios are equal)

b. The three effects of the Donnan effect on the distribution of ions in the body
1. Because of proteins (prot-) in cells, there are more osmotically active particles in cells than in interstitial fluid
(Counteracted by Na-K-ATPase, there is more ions inside due to the concentration gradient of the other anion and the consequent following of cations due to charge)
2. Membrane potential
(<- Asymmetric distribution of ions)
3. Donnan effect on ion movement across the capillary wall since there are more proteins in plasma than in interstitial fluid

(Ganong)

Front 5

Forces acting on ions
a. Equilibrium potential for an ion
b. Nernst equation at 37C
c. Equilibrium potentials for Na, K, and Cl

Back 5

a. Equilibrium potential for an ion
I. The membrane potential at which influx and efflux of the ion are equal

b. Nernst equation at 37 C
Ex = 61.5 log ([Xi]\[Xo])
(Xi = X inside, Xo = X outside)
('Full Nernst equation - Ex = (RT\FZx) x ln ([Xi]\[Xo]). R - gas constant, T - absolute temperature, F - Faraday number (number of coulombs per mole of charge), Zx - valence of X (-1))

c. Equilibrium potentials
I. Na +60 mV
II. K -90 mV
III. Cl -70 mV

(Ganong)

Front 6

Cell membrane
a. General size
b. Phospholipids
c. Proteins - Average % of mass of cell membrane
d. Proteins - Structural types, Functional types

Back 6

a. 7.5 nm

b. Phospholipids
1. Phosphatidylcholine\Lecithin
2. Phosphatidylethanolamine

c. 50%
(But phospholipids weigh about 1\50 of a protein molecule -> 50 phospholipids\protein)

d. Proteins
1. Structural division
I. Integral - Cross membrane
II. Peripheral - Attached to one side only
(Many (alkaline phosphatase, many antigens, many CAMs) are attached to glycosylphosphatidylinositol (GPI) anchors)
(Some proteins are lipidated - they are attached to specific lipids in the cell membrane - myristolated (C14), palmitoylated (C16), prenylated (attached to geranyl-geranyl or farnesyl groups - cholesterols))

2. Functional classification
I. Cell adhesion molecules - Neighbors, basal lamina
(5 classes - integrins, adhesion molecules of the IgG superfamily, cadherins, (Ca-dependent), selectins (lectin-like domains, bind carbohydrates)
II. Pumps
III. Ion channels
IV. Receptors
V. Enzymes
VI. Immune functions

(Ganong)

Front 7

Peroxisomes
a. Size, part of which centrifugal fraction
b. PPARs - What, subtypes
c. Pharmacological agents working on PPARs

Back 7

a. 0.5 mm, microsomal fraction
(Contain over 40 enzymes, which operate in concert with enzymes outside the peroxisome to catalyze a variety of anabolic and catabolic reactions)

b. Peroxisome-proliferator activated receptor (PPAR)
I. Members of the nuclear receptor superfamily
(Which include receptors for steroid and thyroid hormones, activate mRNA production)
II. 3 subtypes -
1. Alpha - Activated by fasting and increase energy-producing enzyme activity
2. Beta
3. Gamma - Activated by feeding and initiate increases in enzymes involved in energy storage

c.
I. Thiazolidinediones\glitazones are agonists for PPAR-gamma (Increase sensitivity to insulin - Hypoglycemics. Ie rosiglitazone, pioglitazone)

II. Fibrates are ligands for PPAR-alphas
(Fibrates are used to lower circulating triglycerides, gemfibrozil, clofibrate, fenofibrate)

(Ganong)

Front 8

Molecular motors
a. Types
b. Which moves toward the + ends of microtubules
c. Which is responsible for the beating of flagella and cilia

Back 8

a. Types
I. Microtubule-based -
1. Kinesin
2. Dyneins
II. Actin-based - Myosins (I-V)

b. Kinesins
(-> Dynein have the other function, moving toward - end of microtubules)

c. (Axonemal) dynein
(Cilia have nine doublets (not triplets like in centrioles) and a pair of microtubules in the center. They are anchored to a basal granule with similar structure as centrioles (9 triplets))

(Ganong)

Front 9

Gap junctions
a. Components
b. Transport substances with a molecular weight up to

Back 9

a. One connexon from each cell unite, each connexon is made up of 6 connexin protein subunits.

b. 1000
(2 nm, -> ions, sugars, amino acids..)

(At least 20 different genes codes for connexin in humans. Its not just a passive process. The X-linked Charcot-Marie-Tooth disease is a peripheral neuropathy associated with mutation of one particular connexin gene)

(Ganong)

Front 10

The genome
a. Total base pairs
b. Number of genes
c. Chromatin
d. How many % of the genome is made up of exons
e. What is the basis of DNA fingerprinting

Back 10

a. 3 x 10^9
(2 m if uncoiled)

b. 30 000
(However its postulated to be as many as 85 000 mRNA)

c. Chromatin
I. The complex of DNA and proteins in the nucleus

d. 3%

e. DNA fingerprint
I. Structural variability in DNA manifests as, among other things, variable repetitions of base pairs (tandem repeats) from one to hundreds of times
II. Cutting the DNA with restriction enzymes demonstrates restriction fragment length polymorphism (RFLP) which is the basis of DNA fingerprint

(Ganong)

Front 11

Regulation of gene expression
a. Gene expression is regulated by cis and trans regulation. What is this
b. It is common for stimuli such as neurotransmitters to initiate chemical events that activate immediate-early genes - what is the steps

Back 11

a. Gene regulation
I. Cis - Regulation from the same gene, promoter region (TATA-box) promote orderly transcription of the gene of which they are a part of
II. Trans - by other gene via transcription factors
(Include steroid hormone receptors and many other factors, 80% are zinc fingers, leuzine zippers, helix-turn-helix or helix-loop-helix motifs)

b.
1. Neurotransmitter ->
2. Second messenger ->
3. Increase transcription of Immediate-early genes: c-Fos and c-Jun -> transcription factors with same name
4. These forms homo- or heterodimer transcription factors that bind to a specific DNA regulatory sequence called an activator protein-1 (AP-1) site - Some of the dimers enhance transcription while others inhibit it
(The appearance of c-Fos, c-Jun, and related proteins is such a common sign of cell activation that immunocytochemistry for them or measurement of their mRNA is used to determine which cells in the nervous system and elsewhere are activated by particular stimuli)

(Ganong)

Front 12

Posttranslational modification
a. Modifications
b. How is a protein being produced transferred into the ER
c. Association with peptide hormones

Back 12

a. Posttranslational modifications
1. Glycosylation
2. Hydroxylation
3. Carboxylation
4. Phosphorylation
5. Cleavage

b.
1. Signal peptide on the amino terminal of the protein being produced
2. A signal recognition particle (SRP) binds to the signal peptide and stops translation until it binds to a translocon, a pore in the endoplasmic reticulum
(SRP is made up of polypeptides and a small RNA)
3. The signal peptide leads the growing chain into the cavity of the ER
(4. The signal peptide is cleaved by a signal peptidase while the rest of the protein is being synthesized)

c. Most peptide hormones are produced as preprohormone, which become prohormone after the signal peptide has been cleaved and hormone after another cleavage
(Ie preproparathyroid hormone)
(Ganong)

Front 13

Apoptosis
a. Examples of physiological apoptosis
b. Examples of pathological
involvement of apoptosis
c. The final common pathway bringing about apoptosis is activation of ...
d. Ligands that activate apoptosis

Back 13

a. Physiological apoptosis
1. Regression of duct systems in the course of sexual development in the fetus
2. Enterocytes that gets 'sloughed off' from the basal lamina and neighboring cells
3. Neurons during development
4. Inappropriate clones of immunocytes

b. Pathological apoptosis
1. Autoimmune diseases
2. Degenerative diseases

c. Caspases
(Cysteine proteases, -> DNA fragmentation, cytoplasmic and chromatin condensation, cell membrane bleb formation)

c. Apoptosis ligands
1. Fas
(Transmembrane protein found on NK cells and T lymphocytes)
2. TNF

(smac\DIABLO and cytochrome C is important components, cytochrome C forms apoptosome with other proteins)

(Ganong)

Front 14

Vesicular transport in cells
a. Mechanism for targeting of vesicles
b. Example
c. Endocytosis - Types

Back 14

a. Targeting of vesicles
I. SNAREs (Soluble N-ethylmalemite-sensitive factor attachment receptor) play an important role. Vesicle SNAREs (v-SNAREs) and target SNAREs (t-SNARES) interact like lock-and-key

b. Examples
1. Mannose-6-Phosphate for transport to lysosome
(Mannose-6-phosphate receptors (MPR)
2. Asn-Pro-any amino acid-Tyr -> Endosome

c. Endocytosis
(1. Constitutive endocytosis
I. Not a specialized process)

2. Clathrin-mediated endocytosis
(I. Occur at membrane indentations where clathrin accumulates
(Clathrin is helped by dyamin\pinchase)
II. Responsible for the internalization of many receptors and the ligands bound to them - LDL, nerve growth factor)

(Ganong)

Front 15

Ion channels
a. Tetrodoxin (TTX) and saxitoxin (STX) - What, use
b. Epithelial sodium channels (ENaCs) - Synonym, location, regulated by

Back 15

a. Tetrodotoxin (TTX) and saxotoxin (STX)
I. Toxins that bind to certain Na channels and block them
II. The number and distribution of Na channels can be determined by tagging them with labeled TTX or STX and analyzing the distribution

b. Epithelium sodium channels (ENaCs)\Amiloride-inhibitable Na channels
I. Apical membranes of epithelial cells in the kidneys, colon, lungs and brain
III. Regulated by aldosterone
(3 subunits - alpha, beta, gamma, only alpha transport Na. Inhibitable by the diuretic Amiloride)

(Ganong)

Front 16

Na-K-ATPase
a. Subunits
b. Binding sites
c. Regulation

Back 16

a. Subunits
I. Alpha
(100 kD, Na and K transport occur through alpha)
II. Beta
(55 kD, alpha and beta have at least 3 different types (alpha 1-3 and beta 1-3) which is expressed in different amounts in different tissues)

b. Binding sites
1. Intracellularly
I. Na binding site
II. Phosphorylation site
(Receive P of ATP)
III. ATP-binding site

2. Extracellular portion
I. K binding site
II. Ouabain binding site
(A glycoside, inhibitory, also binds digitalis glycosides. Digitalis glycosides are inotropic by secondarily inhibiting the Na(3)-Ca(1) antiporter by its effect on Na-K-ATPase)

c. Regulation
1. Increase expression of it - Thyroid hormones, Aldosterone
2. Dopamine inhibit pump by phosphorylating it
(In the kidneys)
3. Insulin increase pump activity

(Use 24% of energy of cells on average, 70% of energy of neurons)

(Ganong)

Front 17

Osmosis
a. Crystalloid vs colloid
b. Oncotic pressure

Back 17

a. Crystalloids are substances that can pass through a semipermeable membrane (ie Na), while colloids cannot (ie plasma proteins)

b. Oncotic pressure
I. The colloid osmotic pressure due to the plasma colloids

(Ganong)

Front 18

Intracellular Ca
a. Intracellular Ca concentration
b. Intracellular storage sites
c. Importing mechanisms
d. Exporting mechanisms
e. Calcium-binding proteins

Back 18

a. 100 nM
(12 000 x in interstitial fluid)

b. Intracellular storage sites
1. Endoplasmic reticulum
2. Mitochondria

c. Importing mechanisms
1. Voltage-gated Ca channels
(Long-lasting (L) and transient (T) depending on whether they inactivate during maintained depolarization)
2. Ligand-gated Ca channels
3. Stretch-activated Ca channels
4. Store-operated Ca channels (SOCC)
(Triggered by depletion of Ca in endoplasmic reticulum, signaling from ER -> plasma membrane is uncertain - maybe mediated by IP3, implied in Alzheimer's and acute pancreatitis)

(5. IP3 receptor - Release Ca from SER)

(6. Ryanodine receptor - Release Ca from SER
I. Skeletal muscle - In response to dihydropyridine receptors (L-type voltage-gated) in T-tubules
II. Cardiac muscle - from increased intracellular calcium\calcium-induced Ca release)

d. Exporting mechanisms
1. Ca-H ATPase
(Antiporter, 2H, 1Ca)
2. Na-Ca ATPase
(Antiporter, 3Na, 1Ca)

e. Calcium-binding proteins
1. Troponin
(Skeletal muscle)
2. Calmodulin
(4 binding sites, triple-methylated amino acid (unique), Ca-Calmodulin can activate myosin light-chain kinase (phosphorylates myosin), phosphorylase kinase (activates phosphorylase), Ca-calmodulin kinase I and II (synaptic function), Calcineurin (phosphatase that inactivates Ca channels, activate T cells, inhibited by calcineurin inhibitors - immunosuppresants (cyclosporin, tacrolimus))
3. Calbindin

(Ganong)

Front 19

Cyclic AMP (cAMP)
a. Formed by
b. The most important resulting cascade, how is it related to altered transcription
c. Degradation - By, pharmacological associations

Back 19

a. Adenylate cyclase, from ATP
(Gs activate, Gi inhibits)
(cholera toxin cause continuous stimulation of adenylate cyclase by inhibiting the GTPase activity of a Gs protein (by transferring an ADP-ribose to a amino acid residue))
(Pertussis toxin stimulate adenylate cyclase by inhibiting Gi (by ADP-ribosylation of Gi))

b. The most important resulting cascade
I. Activate protein kinase A
(PKA activate phosphorylase kinase in the liver by epinephrine via cAMP)
II. PKA phosphorylates the transcription factor cAMP-responsive element-binding protein (CREB)
(Response element - regulatory region on DNA)

c. Degradation
I. Phosphodiesterase
II. Methylxanthines (theophylline, caffeine) inhibits phosphodiesterase and thus increase or prolong the action of cAMP

(Ganong)

Front 20

Cyclic GMP (cGMP)
a. Effects
b. Produced by

Back 20

a. Effects
1. Important in vision in rods and cones
2. cGMP-regulated ion channels
3. cGMP activated cGMP-dependent kinases

b. Produced by guanylate cyclases - 2 classes
1. Transmembrane form
I. Extracellular receptor domain
(2 for ANP, 1 for guanylin (GI polypeptide) which E. coli enterotoxin works on)
II. Cytoplasmic part with tyrosine kinase-like and guanylyl cyclase catalytic activity

2. Intracellular\Cytoplasmic form
I. Soluble
II. contains heme
III. Activated by NO

(Ganong)

Front 21

Growth factors
a. Structure
b. The three groups with examples
c. The most frequent receptor type in the first group

Back 21

a. Polypeptides

b. Growth factors
1. Agents that foster the multiplication or development of various types of cells
I. NGF
II. IGF-1
III. Activins (placental hormone) and inhibins
IV. EGF
(< 20)

2. Cytokines
(< 20, produced by macrophages and lymphocytes, important in regulation of the immune system)

3. Colony-stimulating factors

(Regulate proliferation and maturation of red blood cells and white blood cells)

c. Single membrane-spanning, intracellular tyrosine kinase
(EGF, PDGF.. The tyrosine kinase autophosphorylates itself, some receptors dimerize when they bind and cross-phosphorylate each other)
(One pathway lead via ras proto-oncogene (small G protein) -> mitogen-activated protein (MAP) kinases -> transcription factors -> altered gene expression)

(Many of the cytokines and CSF's activate Janus tyrosine kinases (JAKs) in the cytoplasm -> phosphorylate and activate signal transducer and activator of transcription (STAT) (transcription factors)), other act via serine-threonine kinases -> SMADs (transcription factors)

(Ganong)

Front 22

Aging - The 3 most common theories

Back 22

Aging
1. Tissue age as a result of random mutations in the DNA of somatic cells, with consequent introduction of cumulative abnormalities
(In Werner's syndrome characterized by rapid aging, the genetic abnormality is a mutation of a gene coding for DNA helicase. Mice that have telomerase mutations also age rapidly and share many of the characteristics with humans suffering from Werner's syndrome)
(Also large accumulation in mitochondrial DNA which could lead to defective energy production or increases in free radicals in cells)

2. Cumulative abnormalities are produced by increased cross-linkage of collagen and other proteins, possibly as the end result of the nonenzymatic combination of glucose with amino groups on these molecules

3. Aging is the cumulative result of damage to tissues by free radicals formed in them
(Species with longer life spans produce more superoxide dismutase)
(Decreased caloric intake prolongs life in many experimental animals. This could be due to decreased metabolism -> decreased formation of protein cross-links and decreased production of free radicals)

(Ganong)