Exam 1 Flashcards
Cell
*Cells are the basic structural
and functional units of life.
All living organisms are cellular
in nature,
e.g.: amoebas with only one cell
or human, animals and big plants
with many cells (multicellular).
*There are 50 to 100 trillion cells
in the human body.
Cells have 3 main regions
1- Plasma membrane
2- Cytoplasm
3- Nucleus
Plasma membrane (plasmalemma)
Is the outer thin and flexible membrane of the cell which separates
the intracellular from extracellular compartment (fluid).
Cell membrane protects the cell from trauma
Contains proteins
Structure of the plasma membrane
Membrane is made of a double layer of lipids such as phospholipids, cholesterol and glycolipids, within which proteins are embedded.
Contains integral proteins
used for endocrine hormones
(clinical point) any change or mutation to receptor structure then receptor may so resistance to endocrine hormone and hormone receptor can not bind to receptor
leads to different issues such as type 2 diabetes because the insulin receptor can not accept the insulin hormone which leads to hyperglycemia
Periphreal proteins from inside cell membrane to outside function is to separate the cell membrane from cytoplasm
Phospholipids
Are the most abundant lipids in the
plasma membrane.
The heads are hydrophilic (attached to
water, the main constituent of intra- and
extracellular fluids) and lie along the
inner and outer face of the membrane.
The tails are hydrophobic (avoid water
and line up in the center of the membrane).
Heads are hydrophilic
Tail is hydrophobic(or lipophilic)
Membrane proteins:
1- Integral proteins
2- peripheral proteins
1- Integral proteins
2- peripheral proteins
Membrane proteins:
1- Integral proteins
Are the most abundant proteins in the membrane, most extend entirely through the membrane (transmembrane) but some protrude from one side of the membrane. Could act as receptors.
Membrane proteins:
2- peripheral proteins
are mainly on
the cytoplasmic side.
They support the cytoplasmic side of
the membrane by a network of filaments
Membrane proteins:
Glycocalyx(sugar covering or cell coat):
is a short chain of carbohydrate (sugars)
projected out from the external surface
of glycoproteins or glycolipids.
This functions in cell-to-cell binding and
recognition.
Functions of the plasma membrane
1- Serves as an external cell barrier against substances
and forces outside the cell.
2- Externally facing proteins act as receptors (for hormones,
neurotransmitters etc.) and in cell to cell recognition.
3- Acts in transport of substances into or out of the cell.
The membrane is a selective permeable barrier, allowing
some substances to pass between intra- and extracellular
fluids while preventing others.
Movements of the substances across
the plasma membrane:
- Passive Transport
- Active Transport
- Vesicular or bulk transport
(clinical point) – any modification to active transport(or ion pump) can impact the cellular activity
can impact the action potential
Movements of the substances across
the plasma membrane:
- Passive Transport
1- Passive process: substances can pass freely through the lipid bilayer
down their concentration gradient i.e.: from more concentrated region
to the less concentrated region. No energy (ATP) is needed.
Diffusion: movement of small, uncharged molecules like oxygen, Co2
and fat soluble molecules across the membrane.
Movements of the substances across
the plasma membrane:
- Active Transport
2- Active process: substances move against a concentration gradient from
a lower to a higher concentration, ATP is needed.
Active transport: most larger water-soluble or charged
molecules, such as glucose, amino acids and ions are transported
by a pump or carrier and involve the integral proteins.
Movements of the substances across
the plasma membrane:
- Passive Transport
- Active Transport
- Vesicular or bulk transport
3- Vesicular or bulk transport: Large particles and macromolecules pass
through the membrane by this mechanism. There are generally two types
of bulk transport: exocytosis and endocytosis.
Exocytosis:
Membrane-lined cytoplasmic vesicles fuse with the plasma membrane and release their contents to the outside of the cell. e.g.: mucus and protein secretions from the glands in the body.
Proteins extending from the vesicle membrane vSNAREs, bind with plasma membrane proteins, the tSNAREs (t for target), this causes the lipid layers of the vesicle and cell membrane to join together.
Some cells produce things like hormones
Vesicles cover the hormones(orange circles)
The vesicle fuses to cell membrane then releases the package(hormone) into the blood stream
Endocytosis:
Brings large molecules into the cell, through an initial infolding part of the
plasma membrane that encloses them to form cytoplasmic vesicles.
Clathrin protein, found on the cytoplasmic side of the infolding is
responsible for deforming the membrane.
There are 3 types of endocytosis:
phagocytosis, pinocytosis and receptor-mediated endocytosis.
Endocytosis:
phagocytosis(cell eating):
Here, parts of plasma membrane form pseudopodes and flow around large
molecules such as bacteria or cellular debris and engulf it.
By this way, a membranous vesicle, called a phagosome is formed.
Phagosomes mostly fuse to the lysosomes for enzymatic break down of
phagosomal contents.
White blood cells have such phagocytic activity.
Endocytosis:
pinocytosis(cell drinking):
Is fluid phase endocytosis.
In pinocytosis, a small infolding of the plasma membrane surrounds
a small quantity of extracellular fluid containing dissolved molecules.
This is the main function of cells lining the small intestine, absorption
of the nutrients.
Absorption of fluid
Small intestine
90% of absorption and digestion of fluids, nutrients occur here
Endocytosis:
receptor-mediated endocytosis
It is a selective mechanism. Specific molecules such as insulin and other hormones, enzymes and low density lipoproteins (LDL, molecules that carry cholesterol in the blood to the body’s cells) are brought into the cells by first attaching to a receptor on the membrane before being taken into the cells in a protein coated vesicle.
Contents of the vesicles are released by binding to lysosomes and the
receptors are recycled back to plasma membrane.
Viruses and some toxins use the same mechanism to enter the cells.
Endocytosis:
receptor-mediated endocytosis
LDL and Cholesterol
Receptor(first molecule) grabs the second molecule
LDL uptakes the cholesterol from blood stream then it binds two cholesterol then carries it to the target cell
LDL needs to bind to LDL receptor on cell membrane then it is able to release cholesterol into cell
Cholesterol is the precursor of sex hormones
(clinical point) if there is any modification to LDL receptor then LDL can not bind to LDL receptor(rejected by LDL receptor) and it can not release cholesterol into target cell
testicle with no cholesterol will not be able to produce testosterone
leads to sex hormone disorders
Vitamin D precursor is cholesterol as well
Deficiency in vitamin D leads to osteroperosis
Familial hypercholesterolemia
Is an inherited disease in which the cells lack the receptors that bind to
cholesterol binding LDLs.
As a result, cholesterol cannot enter the cells and builds up in the blood,
causing hypercholesterolemia and atherosclerosis which lead to stroke or
myocardial infarction.
Cholesterol is not able to enter cells which allows cholesterol to build up in blood stream
leads to formation of blood clots -> closure of vessel -> strokes, heart attacks etc
The Cytoplasm
Cytoplasm is the cellular region between the nucleus and plasma membrane.
It consists of:
cytosol, or cytoplasmic matrix which is a viscous fluid containing water,
ions and enzymes, inclusions containing stored nutrients and pigments and organelles.
Ribosomes
- Are dark staining granules with no membrane.
- Ribosomes are site of protein production.
They consist of two subunits:
protein and ribosomal RNA (rRNA, ribonucleic acid).
Free ribosomes make the protein used in the cytosol.
Ribosomes attached on the surface of rER make the proteins used for cell membrane
or exported out of the cell.
Amino acids on the ribosomes are linked together to form protein. This process is
called Translation and is dictated by DNA of the nucleus. Such instructions are
carried to the ribosomes by messengers called messenger RNA (mRNA).
Rough Endoplasmic Reticulum (rER):
1
Is a ribosome-studded system of membrane-walled envelopes in cytosol, called cisternae.
Rough Endoplasmic Reticulum (rER):
2
Ribosomes on the rER make proteins which enter the cisternae and are secreted
by the cell in vesicles.
Ribosomes also make the proteins of the cell membrane.
Smooth Endoplasmic Reticulum (sER):
Is a network of membranous system of sacs and tubules in the cytosol.
It has no ribosomes and is involved in the synthesis of lipids and steroids,
lipid metabolism and drug detoxification.
The precursor of steroids is cholesterol
Golgi apparatus
Is a stack of 3-10 disc-shaped envelopes or cisternae which are bound by membrane.
Cisternae have a cis (convex) and a trans (concave) face.
It sorts the products of rER and packs them in membrane bound vesicles and sends
them to their proper destination.
Secretory granules and lysosomes also arise from the Golgi apparatus.
The last station of the production of proteins
Mitochondria
Are rod like organelles covered by two membranes in the cytoplasm.
The inner membrane is folded into projections called cristae.
Mitochondria are the main energy generator of the cell and are the
main site of ATP synthesis.
Lysosomes
Are spherical, membrane-walled sacs containing digestive enzymes called
Acid hydrolases.
Lysosomes are site of intracellular digestion and they destroy (digest)
deteriorated organelles and substances brought into the cells by vesicles.
They fuse with phagosomes and empty their enzymes into phagosomes,
breaking down their contents. Phagocytic cells have a lot of lysosomes.
Lysosomes
Tay-sachs disease
Tay-Sachs disease is a fatal genetic lipid storage disorder in which harmful quantities of a fatty substance called ganglioside GM2 build up in tissues and nerve cells in the brain.
Infants lack specific enzymes in the
lysosomes responsible for break down of
certain glycolipids. As a result, glycolipids
accumulate in the cell membrane specially
on neurons, resulting in mental retardation,
blindness, spastic movements and death
within 1.5 years from birth.
(clinical point)
deficiency of Acid hydrolase leads to the inability of degradation of large molecules. Glycolipids in brain can cause mental retardation or death in newborns
Tay-sachs disease
Gaucher’s disease
The lack of the glucocerebrosidase enzyme causes harmful substances to build up in the liver, spleen, bones, and bone marrow. The substances prevent cells and organs from working properly.
Symptoms
Symptoms vary depending on the type of disease, but may include:
Bone pain and fractures
Enlarged spleen
Enlarged liver
Lung disease
Seizures
Gaucher’s disease
Type 1
Type 1 disease is most common. It involves bone disease, anemia, an enlarged spleen and thrombocytopenia. Type I affects both children and adults.
Gaucher’s disease
Type 2
Type 2 disease usually begins in infancy with severe neurologic involvement. This form can lead to rapid, early death.
Gaucher’s disease
Type 3
Type 3 disease may cause liver, spleen, and brain problems. Patients may live into adulthood.
Peroxisomes
Are membrane-walled, enzyme-containing sacs.
They contain oxidase and catalase enzymes.
Oxidases use oxygen to neutralize aggressively reactive substances called
free radicals, by converting them to hydrogen peroxide.
Hydrogen peroxide, although reactive and dangerous, it is converted to oxygen
and water by catalases which break down poisons like alcohol, phenol and
formaldehydes that have entered the body. Liver and kidney have many peroxisomes.
---- For detoxification(alcohol etc)
Cytoskeleton (cell skeleton):
Is a network of rods running throughout the cytosol to support the cellular structure
and generates movements of the cell. There are 3 types of such cytoskeleton:
Microtubules, microfilaments and intermediate filaments
Microfilaments are proteins
actin and myosin in muscles control the contractions
Intermediate filaments
tough and gives shape to cell and protects cell from external trauma
Microtubules
involved in cell division
Cytoskeleton
Microtubules
Are cylindrical structures made of tubulin proteins. They radiate out from the
centrosome region close to the nucleus. They give the cell its shape and they organize
the distribution and transport of various organelles within the cytoplasm.
Cytoskeleton
Microfilaments
Are fine filaments of contractile protein called actin. They are labile.
Actin interacts with another protein called myosin, and generates contractile forces
within the cell. It is involved in muscle contraction, and other types of cellular
movements such as amoeboid movements and extension of pseudopods.
Cytoskeleton
Intermediate Filaments
are tough insoluble and stable protein fibers
which act to resist tension placed on the cell.
Centrosome and Centrioles
Centrosome is a spherical structure in the
cytoplasm near the nucleus. It consists of
an outer cloud of protein called: matrix
and an inner pair of centrioles.
Matrix protein is involved in the elongation
of microtubules and mitotic spindle of
microtubules radiates from it in dividing
cells.
Cytoplasmic inclusions
Impermanent structures in the cytoplasm
such as lipid droplets and glycogen
containing glycosomes.
Centrioles:
are in the core of centrosome.
These are paired cylindrical bodies
perpendicular to one another and each
composed of nine triplets of microtubules.
They organize a microtubule network
during mitosis to form the spindle and asters. They also form the bases of cilia
and flagella
The nucleus:
Nucleus is the control center of the cell
and contains genetic materials (DNA),
which directs the cell’s activities by
providing the instructions for protein
synthesis.
Most cells have one nucleus in the center,
some have multiple nuclei e.g.: skeletal
muscle, however, mature red blood cells
have no nucleus (anucleate) at all.
The nucleus:
Parts
1- Nuclear envelope
2- Chromatin and chromosomes
3- Nucleoli
Nucleoli(us)
ribosome producing machine
Nuclear envelope
protects nucleus
connected to lumen of endoplasmic reticulum and release ribosomes
Nuclear envelope:
Surrounds the nucleus and has pores and
is continuous with endoplasmic reticulum.
Nucleolus:
Is a dark staining body within the nucleus.
It contains parts of chromosomes and is
cell’s ribosome producing machine (has
genes that code for rRNA).
Chromatin and chromosomes:
Chromatin is the granular thread-like
material in the nucleus composed of DNA
(Deoxyribonucleic acid)
and histone proteins.
DNA constitute the genes.
genetic code is copied onto mRNA in a
process called transcription.
Deoxyribonucleic acid (DNA):
DNA molecule in chromatin is a double
helix chains of nucleotide molecules.
Nucleotides consist of sugar, phosphate and
one of four bases: thymine (T), adenine (A),
cytosine (C) or guanine (G), which bind to
hold the DNA helix together like a ladder.
DNA helix wraps around clusters of eight
spherical proteins called histones, which
regulate gene expression and transcription.
**Each cluster of DNA and histones is called
a nucleosome. **
Nucleosome
combination of DNA and histones
44 somatic chromosomes
2 sex chromosomes
XX female
XY male
Chromosomes
*Chromosome contains a single, very long
molecule of DNA. There are 46 chromosomes
in a typical human cell.
*Chromatin is distributed in chromosomes.
During cell division, the chromatin is highly
coiled, making the chromosomes appear as
thick rods.
The Cell Life Cycle
The cell life cycle is a series of changes
a cell experiences from the time it forms
until it reproduces itself.
The cycle has two major periods:
1- Interphase, in which the cell grows
and carries on its usual activities,
2- Cell division (mitotic phase), during
this period, the cell divides into 2 cells.
*Cell division is essential for growth and
repair of the body.
The Cell Life Cycle
Interphase
Is the non-dividing phase of the cell cycle,
cells maintain their life-sustaining activities
and prepare for the next cell division.
It consists of subphases G1, S and G2.
G1 (gap 1):
cells are active and grow vigorously and
centrioles start to replicate.
S (synthetic) phase:
DNA replicates itself for the future two
daughter cells having identical genetic
material.
G2 (gap 2):
Enzymes needed for cell division are
synthesized, centrioles finish replication
and cell gets ready to divide.
Cell division or Mitosis
Has four stages: 1- prophase 2- metaphase 3- anaphase 4- telophase
Cell division or Mitosis
- Prophase
**
*Asters (stars) are formed; these are microtubule arrays, extending from the centrosome.
*Chromosomes are formed from coiling and condensation of the chromatin threads.
(each chromosome has 2 identical chromatin threads, now called chromatids;
the chromatids are held together by centromere and a protein complex called cohesin.)
*nucleoli disappear *centriole pairs separate *nuclear envelope fragments
*microtubules disassemble and are newly assembled to form mitotic spindles which lengthen
and push the centrioles farther apart to the poles of the cell (some of these spindles are
attached to chromosomes and are called kinetochores; others are called polar spindles).
**
Some microtubules are connected to chromosomes which is called
kinetochores(know it)
Cell division or Mitosis
- Metaphase
**
*Chromosomes cluster at the middle of the cell,
to form a metaphase plate.
**
*Separase, an enzyme which cleaves
cohesin, start to separates the chromatids.
Cell division or Mitosis
- Anaphase
- *
- the V-shaped chromatids are pulled apart
- *
by the kinetochore spindles to become the
chromosomes of the daughter cells, and the
polar spindles still push against each other
to elongate the cell.
This stage lasts for few minutes only.
Cell division or Mitosis
- Telophase
*This phase is like prophase in reverse.
*chromosomes at the opposite sides of the cell
uncoil and resume extension of the chromatin.
*nuclear envelope forms by rER.
*nucleoli appear
**
**For a short period, the cell has 2 nuclei until
it is completely separated by the process of
CYTOKINESIS.
**
Meiosis
Meiosis is a specialized process of cell division that occurs only in the production of gametes. It consists of two divisions that result in the formation of four gametes, each containing half the number of chromosomes (23 single chromosomes) and half the amount of DNA (1N) found in normal somatic cells (46 single chromosomes, 2N).
Meiosis I
- Synapsis: pairing of 46 homologous duplicated chromosomes.
- Crossing over: large segments of DNA are exchanged.
Alignment: 46 homologous duplicated chromosomes align at the metaphase plate.
Disjunction: 46 homologous duplicated chromosomes separate from each other; centromeres do not split.
Cell division: two secondary gametocytes (23 duplicated chromosomes, 2N) are formed.
For sex chromosomes
During intrauterine life the embryo
(first 8 weeks)
Week 9 until birth is fetus
Know meiosis 1 and 2
Meiosis II
Synapsis: absent
Crossing over: absent
Alignment: 23 duplicated chromosomes align at the metaphase plate.
Disjunction: 23 duplicated chromosomes separate to form 23 single chromosomes; centromeres split.
Cell division: four gametes (23 single chromosomes, 1N) are found.
know meiosis I and II
Clinical Considerations
Aneuploidy, abnormal number of chromosomes, can be trisomy and monosomy
(Clinical point) any mutation or genetic disorder then there may be 22 or 24 chromosomes instead of 23
then this leads to Aneuploidy
genetic disorders possible
Monosomy = 45 total instead of 46
Trisomy = 47 instead of 46
Trisomy 21(Down syndrome)
mother over 40 is at risk for this
(know this)The diagnosis for Down syndrome is by checking a protein in amniotic fluid
alpha-Feto protein
In normal pregnancy the level of hormone is high in first trimester of pregnancy then decreases in 2nd and 3rd trimesters
abnormal the level of protein would increase in second and third trimesters of pregnancy
the elevation is a signal something is wrong
a genetic analysis would be needed to determine what syndrome may be present
Meiotic cell division completes after puberty
Down syndrome
small head, small eyes, big tongue, big nose, shorter than average height
mental retardation possible depending on degree of syndrome
congenital heart disease, speech disorder
organs connected to CNS(eye, ear) are impacted
Klinefelter Syndrome
XXY then technically male but XX dominates the physical look of individual
may have male and female sexual organs but not able to have reproductive capabilities
Turner syndrome
congenital heart disease, possible mental retardation, shorter than average
Gametes
know this.
-contain 23 single chromosomes (22 autosomes and 1 sex chromosome) and 1N amount of DNA.
The term “haploid” is classically used to refer to a cell containing 23 single chromosomes.
- Female gametes contain only the X sex chromosome.
- Male gametes contain either the X or Y sex chromosome; therefore, the male gamete determines the genetic sex of the individual.
Cellular diversity
there are about 200 different cell types in the human body
with a variety of shapes and functions.
Aging:
Aging is complex and may involve cell
**damage due to free radicals **
as a result of normal cell metabolism or cell injury due to radiation and chemical pollutants.
**Mitochondrial theory of aging **
involves a decrease of energy production by
radical-damaged mitochondria which weakens and ages the cell. Vitamins C and E act as antioxidants and prevent excessive production of free radicals. The same is true with caloric intake restriction due to lowering the metabolic rate which slows aging.
Radiation destroys mitochondria, cell membrane, and possibly nucleus
Without mitochondria there is no ATP production which means ion pumps will not function
Releasing of free radicals
vitamin C and E are antioxidants and prevent release of free radicals
**Genetic theories of aging **
proposes that aging is programmed into our genes (senescence).
Apoptosis (Programmed Cell Death)
Apoptosis is the method whereby cells are removed from tissues in an orderly fashion as a part of normal maintenance or during development.
Activation of some cytokines, such as tumor necrosis factor(TNF) stimulates caspase 3 and 9 which are involved in cell death
caspase normally exist inside a cell
activation of caspase may not be enough to destroy all cancer
Too much caspase may be too much causing damage to nerve cells such as Alzheimer disease and stroke
Apoptosis (Programmed Cell Death)
Morphological features
Cells that undergo programmed cell death have several morphological features.
-They include chromatin condensation, breaking up of the nucleus, and the plasma membrane.
The cell shrinks and is fragmented into membrane-enclosed fragments called apoptotic bodies.
Apoptosis (Programmed Cell Death)
Mechanisms
The signals that induce apoptosis may occur through several mechanisms.
Certain cytokines, such as tumor necrosis factor (TNF), may also activate caspases that degrade regulatory and structural proteins in the nucleus and cytoplasm, leading to the morphological changes characteristic of apoptosis.
Apoptosis (Programmed Cell Death)
Contribution to disease
Defects in the process of programmed cell death contribute to many major diseases.
Too much apoptosis causes extensive nerve cell loss in Alzheimer disease and stroke.
Insufficiency of apoptosis has been linked to cancer and other autoimmune disease.
Cancer
A cell mass which divides and multiplies abnormally; it is also called a neoplasm.
Neoplasms are classified as Benign or Malignant.
Cancer
Benign neoplasm
or tumor is a local mass, remains compacted, often encapsulated, grows
slowly and seldom kills the host.
Cancer
Malignant neoplasm or cancer
is a mass which is not-capsulated and grows rapidly.
Cells here are immature and they invade their surrounding.
These give metastasis (invading other tissues) by means of lymphatics and/or blood.
Oncogenes
Oncogenes is cancer
but any mutation of gene structure can lead to cancer
Oncogenes are the result of mutations of certain regulatory genes, called protooncogenes, which normally stimulate or inhibit cell proliferation and development.
Genetic accidents or viruses may lead to the formation of oncogenes.
Oncogenes dominate the normal alleles (proto-oncogenes), causing deregulation of cell division, which leads to a cancerous state.
Bladder cancer and acute myelogenous leukemia are caused by occogenes.
Functions of yolk sac attached to embryo at 4 weeks
- Wall of yolk sac produces stem cells in blood to give nutrients to embryo from mother
- no cord for connection from mom -> baby - Produce and release germ cells
- XX for female
- XY for male
- germ cells migrate to primitive gonads(testicles and ovaries) to start meiotic cell division
- can not complete the process until puberty
sperm ad ovum produced in gonads
Tissues
Tissues are collection of structurally similar cells with related function.
The entire body is composed of only four major types of tissues.
Muscle
Nervous
Epithelial
Connective tissues
Groupings of these four primary tissues into anatomical and functional units are called organs.
Organs in turn, may be grouped together by common functions into systems.
Muscle Tissue
Muscle is contractile tissue of the body and is derived from the mesodermal layer of embryonic germ cells. It is classified as skeletal, cardiac, or smooth muscle, and its function is to produce force and cause motion, either locomotion or movement within internal organs.
Types:
Skeletal
Smooth
Cardiac
Muscle Tissue
Skeletal muscle
is a type of striated muscle, usually attached to the skeleton. Skeletal muscles are used to create movement, by applying force to bones and joints; via contraction.
innervation is motor system
body movement
Muscle Tissue
Smooth muscle
is found within the walls of organs and structures such as the esophagus, stomach, intestines, bronchi, uterus, urethra, bladder, and blood vessels, and unlike skeletal muscle, smooth muscle is not under conscious control.
internal organs(stomach, intestine) the most important part is the blood vessels controls blood pressure innervation is autonomic nervous system
Muscle Tissue
Cardiac muscle
is also an “involuntary muscle” but is a specialized kind of muscle found only within the heart.
in heart innervation is autonomic nervous system difference is full of mitochondria(much more than other smooth muscle areas) for strong contractions by ATP production
Nervous tissue
Nervous tissue is specialized to:
react to stimuli and to conduct impulses to various organs in the body which bring about a response to the stimulus.
Nerve tissue (as in the brain, spinal cord and peripheral nerves that branch throughout the body) are all made up of specialized nerve cells called neurons.
Neurons are easily stimulated and transmit impulses very rapidly.
Axon carries neurotransmitters
to end terminal
Neurotransmitters
chemical substance
stimulatory or inhibitory
epinepherine
Nerve anatomy
A nerve is made up of many nerve cell fibers (neurons) bound together by connective tissue. A sheath of dense connective tissue, the epineurium surrounds the nerve.
This sheath penetrates the nerve to form the perineurium which surrounds bundles of nerve fibers. blood vessels of various sizes can be seen in the epineurium.
The endoneurium, which consists of a thin layer of loose connective tissue, surrounds the individual nerve fibers.
Epineurium externally
Perineurium surrounds bundles
Endoneurium individual nerve fibers
Functions of Epithelial Tissue
- Protection
- Sensation Sensory stimuli
- Secretion In glands
- Absorption
- Excretion
- Diffusion
- Cleaning
- Reduces friction
Functions of Epithelial Tissue
- Protection:
Epithelial cells from the skin protect underlying tissue from mechanical injury, harmful chemicals, invading bacteria and from excessive loss of water.
Functions of Epithelial Tissue
- Sensation Sensory stimuli:
penetrate specialized epithelial cells. Specialized epithelial tissue containing sensory nerve endings is found in the skin, eyes, ears, nose and on the tongue.
Functions of Epithelial Tissue
- Secretion In glands:
epithelial tissue is specialized to secrete specific chemical substances such as enzymes, hormones.
Functions of Epithelial Tissue
- Absorption:
Certain epithelial cells lining the small intestine absorb nutrients from the digestion of food.
Functions of Epithelial Tissue
5.Excretion:
Epithelial tissues in the kidney excrete waste products from the body and reabsorb needed materials from the urine. Sweat is also excreted from the body by epithelial cells in the sweat glands.
Functions of Epithelial Tissue
- Diffusion:
Simple epithelium promotes the diffusion of gases, liquids and nutrients. Because they form such a thin lining, they are ideal for the diffusion of gases (eg. walls of capillaries and lungs).
Functions of Epithelial Tissue
- Cleaning:
Ciliated epithelium assists in removing dust particles and foreign bodies which have entered the air passages.
Functions of Epithelial Tissue
- Reduces Friction:
The smooth, tightly-interlocking, epithelial cells that line the entire circulatory system reduce friction between the blood and the walls of the blood vessels.
Epithelial tissue and glands:
Epithelia are sheets of cells that cover body surfaces and cavities.
Their function is to protect the body
(such as the skin) or sensory reception such as the olfactory epithelial cells, absorption, such as the internal covering cells of the intestine, ion transport and filtration, like the cells covering various tubules in the kidney.
Glands are also covered internally by epithelial cells which function
in secretion of their products.
Classification of the epithelial cells:
Epithelial cells are classified according to their shape into:
1- Squamous (flat)
2- Cuboidal (cube like)
3- Columnar (tall and rod-like)
They are further classified by number of cell layers into:
1- Simple (only one layer), 2- Stratified (multiple layers)
The stratified epithelia are named according to the shape of the apical cells.
Pseudostratified
looks like multiple layers but really one staggered layer
Classification of the epithelial cells:
Simple, stratified, pseudostratified with cilia
Simple: There is a single layer of cells.
Stratified: More than one layer of cells. The superficial layer is used to classify the layer. Only one layer touches the basal lamina. Stratified cells can usually withstand large amounts of stress.
Pseudostratified with cilia: This is used mainly in one type of classification (pseudostratified columnar epithelium). There is only a single layer of cells, but the position of the nuclei gives the impression that it is stratified.
Classification of the epithelial cells:
Simple
There is a single layer of cells.
Classification of the epithelial cells:
Stratified
More than one layer of cells. The superficial layer is used to classify the layer. Only one layer touches the basal lamina. Stratified cells can usually withstand large amounts of stress.
Classification of the epithelial cells:
Pseudostratified with cilia
This is used mainly in one type of classification (pseudostratified columnar epithelium). There is only a single layer of cells, but the position of the nuclei gives the impression that it is stratified.
Simple squamous epithelia
Found in capillary, blood vessels, respiratory
Function: gas exchange and protection of blood vessels
A simple squamous epithelium is characterized by the presence of squamous cells which are all in contact with the basement membrane.
The surface squamous cells are irregularly shaped and very flat; so flat that the cell nucleus sometimes creates a bump in the surface of the cell.
Gases and other substances can easily diffuse across squamous cells to the underlying basement membrane, and because of their smooth surface, liquids can quickly flow over them.
As such, simple squamous epithelia are seen lining body cavities and capillaries to reduce friction, as well as lining the alveoli to facilitate gas exchange.
Simple cuboidal epithelium:
Location: sex organs(ovary, testicle), renal system
Function: Absorption and secretion of hormones and mucus
*Single layer of cubelike cells with large, spherical central nuclei.
Function: secretion and absorption.
Location: Cuboidal epithelium is found in glands and in the lining of the kidney tubules as well as in the ducts of the glands. They also constitute the germinal epithelium which produces the egg cells in the female ovary and the sperm cells in the male testes.
Simple columnar epithelium:
Location: GI(gastrointestinal) tract
Function: secretion of mucus
Columnar epithelial cells occur in one or more layers. The cells are elongated and column-shaped. The nuclei are elongated and are usually located near the base of the cells.
Location:
Columnar epithelium forms the lining of the stomach and intestines. Some columnar cells are specialised for sensory reception such as in the nose, ears and the taste buds of the tongue. Goblet cells (unicellular glands) are found between the columnar epithelial cells of the duodenum.
Function:
They secrete mucus or slime, a lubricating substance which keeps the surface smooth.
Pseudostratified columnar epithelium
Location: large glands, trachea
Function: secretion of mucus
Function: Secretion, mucus.
Location: Ducts of large glands, Ciliated variety lines the trachea, most upper respiratory tract.
Stratified cuboidal epithelia
are multi-layered.
They protect areas such as ducts of sweat glands and the male urethra.
Function: Protection
Stratified columnar epithelium
Are several cell layers.
Function: Protection, secretion
Location: small amount in male urethra and in large ducts of some glands.
Stratified squemous epithelium
Location: vagina
Transitional epithelium
Location: urinary bladder, ureter, urethra
Function: accelerates the urine circulation
Glands:
Glands of the body are classified as either exocrine or endocrine types.
*Exocrine glands are glands that retain ducts to body surfaces.
*Endocrine glands are therefore referred to as “ductless” glands.
Endocrine and exocrine glands secrete various products. These include hormones, enzymes, metabolites, and other molecules.
In exocrine glands, products of these cells collect in the duct of the gland and flow toward the surface to which the duct is in contact.
Since endocrine glands lack ducts, the product is released across the cell membrane into interstitial spaces around the cells. Diffusion of the product into capillaries follows.
Glands:
Exocrine
gland contains a duct which opens into a cavity
sweat/salivary glands
*Exocrine glands are glands that retain ducts to body surfaces.
In exocrine glands, products of these cells collect in the duct of the gland and flow toward the surface to which the duct is in contact.
Glands:
Endocrine
secretes endocrine hormone
released into blood stream
*Endocrine glands are therefore referred to as “ductless” glands.
Endocrine and exocrine glands secrete various products. These include hormones, enzymes, metabolites, and other molecules.
Since endocrine glands lack ducts, the product is released across the cell membrane into interstitial spaces around the cells. Diffusion of the product into capillaries follows.
Glands:
Pancreas
exocrine
pancreatic enzymes for digestion of carbohydrates, lipids, and proteins
endocrine
insulin(decreases blood glucose), glucagon(increases BG), somatostatin(decreases or inhibits insulin/glucagon production)
normal 70-120 mg/dL for blood sugar
somatostatin keeps within this range
Exocrine glands:
Exocrine glands secrete their products onto body surfaces or body cavities.
Goblet cells are examples of mucus secreting unicellular exocrine glands.
Multicellular exocrine glands are classified by the structure of their ducts as
simple, or compound and by the structure of their secretory units as tubular,
alveolar (acinar), or tubuloalveolar
Endocrine glands:
Endocrine or ductless glands secrete hormones, which enter
the circulation and reaches the target tissue to have their effects,
an example is the pancreas which has an endocrine as well as
exocrine parts. The endocrine part produces insulin and glucagon
and other hormones. The exocrine part secretes enzymes responsible
for food breakdown and digestion.
Modes of Secretion of exocrine glands
Secretory cells of exocrine glands release their products into ducts in three different ways.
The mode of secretion can be classified as:
1-merocrine
2-Apocrine
3-holocrine
Modes of Secretion of exocrine glands
Meocrine
Cells that secrete products via the merocrine method form membrane-bound secretory vesicles internal to the cell. These are moved to the apical surface where the vesicles coalesce with the membrane on the apical surface to release the product.
Most glands release their products in way.
Modes of Secretion of exocrine glands
Apocrine
In those glands that release product via the apocrine method, the apical portions of cells are pinched off and lost during the secretory process. This results in a secretory product that contains a variety of molecular components including those of the membrane. Mammary glands release their products in this manner.
Modes of Secretion of exocrine glands
Holocrine
The third type of secretory release, holocrine, involves death of the cell. The secretory cell is released and as it breaks apart, the contents of the cell become the secretory product.
This mode of secretion results in the most complex secretory product. Some sweat glands located in the axillae, pubic areas, and around the areoli of the breasts release their products in this manner. Sebaceous glands also are of this type.
Features of the lateral cell surfaces:
Factors holding epithelial cells together:
1- Adhesion proteins link plasma membranes of adjacent cells
2- Contours of adjacent cell membranes
3- Special cell junctions:
- Tight junctions
- Adhering junctions
- Desmosomes
- Gap junctions
Tight junctions (zona occludens):
Tight junctions, or zonula occludens. It is a type of junctional complex.
They are formed by claudin and occludin proteins, joining the cytoskeletons of the adjacent cells.
Functions:
-They hold cells together
-They block the movement of
integral membrane proteins between
the apical and basolateral surfaces of the cell,
-This aims to preserve the transcellular transport.
-They prevent the passage of molecules and ions
through the space between cells.
Desmosomes :
1- two disc-like plaques connected across intercellular space
2- Plaques of adjoining cells are joined by proteins called cadherins
3- Proteins interdigitate into extracellular space
4- Intermediate filaments insert into plaques from cytoplasmic side
Gap junctions:
1- passageway between two adjacent cells
2- they let small molecules move directly between neighboring cells
3- cells are connected by hollow cylinders of protein
Act as channel for ions
Connexion is name of junction
formed by 6 connexin monomers
When cell membrane receives stimulus from outside then the gap junctions open
The rate of gap junctions is high in myocardium
Features of the basal epithelial surface:
1- Epithelial cells lie on a protein sheet called basal lamina.
2- It acts as a filter and base on which regenerating epithelial cells can grow.
3- The basal lamina and some underlying reticular fibers , form the ticker
basement membrane.
Connective tissue
As the name implies, connective tissue serves a “connecting” function. It supports and binds other tissues. Unlike epithelial tissue, connective tissue typically has cells scattered throughout an extracellular matrix.
Derived from mesoderm.
Loose Connective Tissue -Collagenous Fibers -Elastic fibers -Reticular Fibers Fibrous Connective Tissue
Specialized Connective Tissues
- Adipose
- Cartilage
- Bone
Marfan syndrome
is an autosomal dominant genetic disorder of the connective tissue characterized by disproportionately long limbs, long thin fingers, a relatively tall stature, and a predisposition to cardiovascular abnormalities, specifically those affecting the heart valves and aorta.
Pathogenesis
Marfan syndrome has been linked to a defect in the gene on chromosome 15 which encodes a glycoprotein called fibrillin-1.
Fibrillin is essential for the formation of the elastic fibers found in connective tissue
Chromosome 15(know it) which encodes a glycoprotein called fibrillin-1
fibrillin-1 is for formation of elastic fibers
Can lead to cardia megaly which is bad
Ehlers-Danlos syndrome
is a group of rare genetic disorders affecting humans and domestic animals caused by a defect in collagen synthesis (Collagen I and III).*
Extreme elasticity to skin and joints
No specific gene therapy for this at the moment
Body fluids
In most individuals, approximately 67% of the total weight is water within cells, in the intracellular compartment.
The remaining of 33% of the total body water comprises the extracellular compartment.
About 20% of this extracellular fluid is contained the vessels of cardiovascular system, where it comprises the fluid portion of the blood, or blood plasma.
Extracellular matrix
The extracellular environment fluids, as interstitial, or tissue, fluid, within a matrix of glycoproteins and proteoglycans. It consists of the protein fibers collagen and elastin. This fluid, derived from blood plasma, provides nutrients and regulatory molecules to the cells. The extracellular environment is supported by collagen and elastin protein fibers, which also from the basal lamina below epithelial membranes.
Extracellular matrix
Integrins
are a class of glycoproteins that extend from the cytoskeleton within a cell, through its plasma membrane, and into the exracellular matrix. By binding to components within the matrix, they serve as adhesion molecule between cells and the extracellular matrix.
Categories of transport across the plasma membrane
The mechanisms involved in the transport of molecules and ions through the cell membrane may be divided into two categories:
1) transport that requires the action of specific carrier proteins in the membrane, called carrier-mediated transport, Carrier-mediated transport may be further subdivided into:
a. facilitated diffusion
b. active transport
2) transport through the membrane that is not carrier mediated. It involves the simple diffusion of ions, lipid-soluble molecules, and water through the membrane, Osmosis is the net diffusion of solvent (water) through a membrane.
Passive transport – molecule or ion moves from higher to lower concentrated area without consuming ATP
Active transport – molecule or ion moves from lower to higher concentrated area with ATP
sodium potassium pump
Categories of transport across the plasma membrane
Energy requirements
Membrane transport processes may also be categorized by their energy requirements:
Passive transport is the net movement of molecules and ions across a membrane from higher to lower concentration, it does not require metabolic energy. Passive transport includes simple diffusion, osmosis, and facilitated diffusion.
Active transport is net movement across a membrane that occurs against a concentration gradient (to the region of higher concentration). Active transport requires metabolic energy (ATP) and involves specific carrier proteins.
Simple diffusion
Formula
- Characteristics of simple diffusion-is the only form of transport that is not carrier-mediated.-occurs down and electrochemical gradient (downhill)-does not require metabolic energy and therefore is passive.
- Diffusion can be measure using the following equation:
J= -PA (C1-C2)
where: J=flux (flow) (mmol/sec)P=permeability (cm/sec)A=area (cm2)C1=concentration1 (mmol/L)C2=concentration2 (mmol/L)
3. Permeability-is the P in the equation for diffusion.Describes the ease with which a solute diffuses through a membrane.-depends on the characteristics of the solute and the membrane.
Simple diffusion
a. Factors that increase permeability:
- high oil/water partition coefficient of the solute increases solubility in the lipid of the membrane.
- decrease radius (size) of the solute increases the speed of diffusion.
- decrease membrane thickness decreases the diffusion distance.
b. Small hydrophobic solutes have the highest permeabilities in lipid membranes.
From higher to lower concentration
Concentration of ion
Size of solute
(highly important)Permeability of membrane to the solute or substance
Depends on structure of substance
Steroid hormones(ie sex hormones) will pass more easily through membrane due to high oil concentration lipophilic or hydrophobic
Carrier-mediated transport
- The characteristics of carrier-mediated transport apply to facilitated diffusion and primary and secondary active transport.
1. Stereospecificity. For example, D-glucose (the natural isomer) is transported by facilitated diffusion, but the L-glucose isomer is not. Simple diffusion, however, would not distinguish between the two isomers because it does not involve a carrier.
2. Saturation. The transport rate increases as the concentration of the solute increases, until the carriers are saturated. The transport maximum (™) is analogous to the maximum velocity (V max) in enzyme kinetics.
3. Competition. Structurally related solutes compete for transport sites on carrier molecules. For example, galactose is a competitive inhibitor of glucose transport in the small intestine.
Facilitated diffusion
- Characteristics of facilitated diffusion
-occurs down and electrochemical gradient (downhill), similar to simple diffusion.
-does not require metabolic energy and therefore is passive.
–is more rapid than simple diffusion.
-is carrier-mediated and therefore exhibits stereospecificity, saturation, and competition. - Example of facilitated diffusion
- glucose transport in muscle and adipose cells in downhill is carrier-mediated, and is inhibited by sugars such as galactose, therefore, it is categorized as facilitated diffusion. In diabetes mellitus, glucose uptake by muscle and adipose cells is impaired because the carriers for facilitated diffusion of glucose require insulin.
A molecule or substance helps a second molecule or substance move
(clinical point) any change to insulin receptor OR insulin production by pancreas that lead to deficiency of insulin then leads to hyper glycemia(blood glucose concentration increases)
excess glucose is harmful to cells(diabetes)
Primary active transport
- characteristics of primary active transport
- occurs against an electrochemical gradient (uphill).
- requires direct input of metabolic energy in the form of adenosine triphosphate (ATP) and therefore is active.
- is carrier-mediated and therefore exhibits stereospecificity, saturation, and competition. - Examples of primary active transporta. Na+, and K+ (pump) in cell membranes transports Na+ from intracellular to extracellular fluid and K+ from extracellular to IC fluid, it maintains low intracellular Na+ and high intracellular K+.
- Both Na+ and K+ are transported against their electrochemical gradients.
- Energy (ATP) is provided.
- The stoichiometry is 3 Na+/2 K+.
- Specific inhibitors of Na+, K+-atpase are the cardiac glycoside drugs ouabain and digitals.
b. Ca2+-ATPase (or Ca2+ pump) in the sarcoplasmic reticulum (SR) or cell membrane transports Ca2+ against an electrochemical gradient.
c. H+, K+-ATPase (or proton pump) in gastric parietal cells transports H+ into lumen of the stomach against its electrochemical gradient.
- It is inhibited by omeprazole.
Primary active transport – different types of ions can move against each other through cell member or channels but these ion pumps require ATP to function
2 ions involved(1 in and 1 out)
(clinical point) over secretion of hydrogen ion into gastric lumen leads to irritation of stomach which is gastritis(inflammation/irritation of stomach)
omeprazole is antiacid which will block the proton pump
proton pump inhibitor
no hydrogen ion release into stomach which is treatment for gastritis
Secondary active transport
- Characteristics of secondary active transport
a. The transport of two or more solutes is coupled.
b. One of the solutes (usually Na+) is transported downhill and provides energy for the uphill transport of the other solute(s).
c. Metabolic energy is not provided directly, but indirectly from the Na+ gradient that is maintained across cell membranes. Thus, inhibition of Na+, K+-ATPase will decrease transport of Na+ out of the cell, decrease the transmembrane Na+ gradient, and eventually inhibit secondary active transport.
d. If the solutes move in the same direction across the cell membrane, it is called cotransport, or symport.
Example: Na+-glucose cotransport in the small intestine and Na+-K+-2Cl- cotransport in the renal thick ascending limb.
e. If the solutes move in opposite directions across the cell membranes, it is called countertransport, exchange, or antiport.
Example: Na+-Ca2+ exchange.
After primary transport the ion can transport more than one ion
Sodium pump requires active transport and ATP then sodium can transport other ions(multiple as opposed to just 1 like active transport)
Glucose should be 0% in healthy individuals urine
glucourea = glucose in urine
Moving of ions in same direction is called symport
symporting of other ions
Na+ antiports hydrogen into urine from blood
Osmosis
Osmolarity
is the concentration of osmotically active particles in a solution.
- is a colligative property can be measured by freezing point depression.
- can be calculated using the following equation:
Osmolarity= g x c
Osmolarity=concentration of particles (osm/L)
g=number of particles in solution (osm/mol) (ex: gNaCl=2, gGlucose =1)
c=concentration (mol/L)
- Two solutions that have the same calculated osmolarity are isosmotic.
- If two solutions have different calculated osmolarities, the solution with the higher osmolarity is hyperosmotic and the solution with the lower osmolarity is hyposmotic.
Clinical point – deficiency of Albumin or destruction of capillary leads to formation of edema
edema = accumulation of fluid in cell or intratitial space
not good
Osmosis and osmotic pressure
-Osmosis is the flow of water across a semipermeable membrane from a solution with low solute concentration to a solution with high solute concentration.
- Example of osmosis
a. Solution 1 and 2 are separated by a semipermeable membrane. Solution 1 contains a solute that is too large to cross the membrane. Solution 2 is pure water. The pressure of the solute in solution 1 produces an osmotic pressure.
b. The osmotic pressure difference across the membrane causes water to flow from solution 2 (which has no solute and the lower osmotic pressure) to solution 1 (which has the solute and the higher osmotic pressure.)
c. With time, the volume of solution 1 increases and the volume of solution 2 decreases. - Calculation osmotic pressure (van’t Hoff’s law)
Os=g x C x RT
os=osmotic pressure (mmHg or atm)g=number of particles in solution (osm/mol)C=concentration (mol/L)R=gas constant (0.082 L-atm/mol)T=absolute temperature (K)
Osmosis and osmotic pressure
Calculation osmotic pressure (van’t Hoff’s law)
- Calculation osmotic pressure (van’t Hoff’s law)
Os=g x C x RT
os=osmotic pressure (mmHg or atm)g=number of particles in solution (osm/mol)C=concentration (mol/L)R=gas constant (0.082 L-atm/mol)T=absolute temperature (K)
Osmotic pressure
- The OP increases when the solute concentration increases.
- The higher the osmotic pressure of a solution, the greater the water flow into it.
- Two solutions having the same effective osmotic pressure are isotonic because no water flows across a semipermeable membrane separating them. If two solutions separated by a semipermeable membrane have different effective osmotic pressures, the solution with the higher effective osmotic pressure is hypertonic and the solution with the lower effective osmotic pressure is hypotonic. Water flows from the hypotonic to the hypertonic solution.
- Colloid osmotic pressure, or oncotic pressure, is the osmotic pressure created by proteins (plasma proteins).
Reflection coefficient (RC)
- is a number between zero and one that describes the ease with which a solute permeates a membrane.
a. If the RC is one, the solute is *impermeable. Therefore, it is retained in the original solution, it creates an osmotic pressure, and it causes water flow. Serum albumin (a large solute) has a reflection coefficient of nearly one.
b. If RC is zero, the solute is completely permeable. Therefore, it will not exert any osmotic effect, and it will not cause water flow. Urea (a small solute) has a reflection coefficient of close to zero and it is, therefore, an ineffective osmole.
Calculating effective osmotic pressure
-Effective osmotic pressure is the osmotic pressure (calculated by van’t Hoff’s law) multiplied by the reflection coefficient.
*If the reflection coefficient is one, the solute will exert maximal effective osmotic pressure. If the reflection coefficient is zero, the solute will exert no osmotic pressure.
Calculating effective osmotic pressure
- Effective osmotic pressure is the osmotic pressure (calculated by van’t Hoff’s law) multiplied by the reflection coefficient.
- If the reflection coefficient is one, the solute will exert maximal effective osmotic pressure. If the reflection coefficient is zero, the solute will exert no osmotic pressure.
Cystic fibrosis
CF is as a result of a genetic defect, abnormal NaCl and water movement occurs across wet epithelial membranes.
Where such membranes line the pancreatic ductules and small respiratory airways, they produce a dense, viscous mucus that cannot be properly cleared, which may lead to pancreatic and pulmonary disorders.
The genetic defect involves a particular glycoprotein that forms chloride (Cl-) channels in the apical membrane of the epithelial cells. This protein known as CFTR ( for cystic fibrosis transmembrane conductance regulator) is formed in the usual manner in the endoplasmic reticulum.
It does not move into the Golgi complex for processing, it doesn’t get correctly processed and inserted into vesicles that would introduce it into the cell membrane.
Pathophysiology of CF
Cystic fibrosis occurs when there is a mutation in the CFTR gene. The protein created by this gene is anchored to the outer membrane of cells in the sweat glands, lung, pancreas, and other affected organs.
The protein spans this membrane and acts as a channel connecting the inner part of the cell (cytoplasm) to the surrounding fluid.
This channel is primarily responsible for controlling the movement of chloride from inside to outside of the cell. When the CFTR protein does not work, chloride is trapped outside the cell.
Regulation of blood osmolality
When a person becomes dehydrated, the blood becomes more concentration as the total volume is reduced.
The increased blood osmolality and osmotic pressure stimulate osmoreceptors, which are neurons located in a part of the brain called the hypothalamus.
As a result of increased osmoreceptor stimulation, the person becomes thirsty and if water is available, drinks. Along with increased water intake, a person who is dehydrated excretes a lower volume of urine.
- Increased plasma osmolality stimulates osmoreceptors in the hypothalamus of the brain.
- The osmoreceptors in the hypothalamus then stimulate a tract of axons that terminate in the posterior pituitary; this causes the posterior pituitary to release antidiuretic hormone (ADH) into the blood.
- ADH acts on the kidneys to promote water retention, so that a lower volume of more concentrated urine is excreted.
* Normal osmolality in plasma is about 280 - 303 milli-osmoles per kilogram
After severe dehydration the blood becomes concentrated leading to stimulation of osmoreceptors located on the wall of large blood vessels
CN 9 and CN 10 take the information to CNS(hypothalamus)
CN 9 and CN 10
the central osmoreceptor is stimulated
the nuclei “supraoptic” and “paraventricular” in hypothalamus secrete ADH(antidiuretic hormone)
ADH released into blood stream
blood stream carries ADH to nephron of kidney for water retention
after binding of ADH to V2 receptor the tubule reapportion of fluid by capillary
Conclusion: ADH dilutes concentrated blood by fluid reabsorption(know this)
ADH inhibits dehydration
it decreases blood osmotic pressure by dilution of blood
Edema
Water returns from tissue fluid to blood capillaries because the protein concentration of blood plasma is higher than the protein concentration of tissue fluid. Plasma proteins, in contrast to other plasma solutes, cannot pass from the capillaries into the tissue fluid.
Therefore, plasma proteins are osmotically active. If a person has an abnormally low concentration of plasma proteins, excessive accumulation of fluid in the tissues- a condition called edema will result.
This may occur, for example, when a damaged liver as in cirrhosis is unable to produce sufficient amounts of albumin, the major protein in the blood plasma.
Hyperglycemia
The kidneys transport a number of molecules from the blood filtrate which becomes urine, back into the blood. Glucose, for example in normally completely reabsorbed so that urine is normally free of glucose. If the glucose concentration of the blood and filtrate is too high a condition called hyperglycemia. However, the transport maximum will be exceeded. In this case, glucose will be found in the urine (glycosuria). This may result from the consumption of too much sugar or from inadequate action of the hormone insulin in the disease diabetes mellitus.
Hyperglycemia – blood glucose more than 120mg
Hypoglycemia
The rate of the facilitated diffusion of glucose into tissue cells depends directly on the plasma glucose concentration. When the plasma glucose concentration is abnormally low- is called hypoglycemia.
Hypoglycemia – blood sugar is below 50mg
Oral rehydration therapy
The therapy is effective for diarrhea because:
- The absorption of water by osmosis across the intestine is proportional to the absorption of Na+.
- The intestinal epithelium cotransports Na+ and glucose.
The glucose in the mixture promotes the cotransport of Na+ and the Na+ transport promotes the osmotic movement of water from the intestine into the blood.
Add salt and sugar to water
Diffusion potential
A. Ion channels
- are integral proteins that span the membrane and, when open, permit the passage of certain ions.
- Ion channels are selective; they permit the passage of some ions, but not others. Selectivity is based on the size of the channel and the distribution of charges that line it.
- Ion channels may be open or closed. When the channel is closed, ions cannot flow through.
- The conductance of a channel depends on the probability that the channel is open. The higher the probability that a channel is open, the higher the conductance, or permeability. Opening and closing of channels are controlled by gates.
a. Voltage-gated channels are opened or closed by changes in membrane potential. - The activation gate of the Na+ channel in nerve is opened by depolarization; when open, the nerve membrane is permeable to Na+.
- The inactivation gate of the Na+ channel in nerve is closed by **repolarization; when closed, the nerve membrane is impermeable to Na+ (e.g., during the repolarization phase of the nerve action potential).
B. Ligand-gated channels (open or closed by hormones, second messengers, or neurotransmitters.
The cell membrane contains ion channels
some channels are gated(open and close)
Action potential
when cell membrane receives stimulus from outside leads to opening of some ion channels such as sodium(Na+)
Na+ enters into cell then it leads to depolarization of that cell
the cell shows reaction to the stimulus(aka action potential)
Diffusion and equilibrium potentials
-A diffusion potential is the potential difference generated across a membrane because of a concentration difference of an ion.
-A diffusion potential can be generated only if the membrane is permeable to the ion.
–the size of the diffusion potential depends on the size of the concentration gradient.
-The sign of the diffusion potential depends on whether the diffusing ion is positively or negatively changed.
-Diffusion potentials are created by the diffusion of very few ions and therefore, do not result in changes in concentration of the diffusing ions.
-The equilibrium potential is the diffusion potential that exactly balances (opposes) the tendency for diffusion caused by a concentration differences. At electrochemical equilibrium, the chemical and electrical driving forces that act on an ion are equal and opposite, and more net diffusion of the ion occurs.
- Example of a Na+ diffusion potential (NaCl)
- Example of a Cl- diffusion potential
Diffusion and equilibrium potentials (continued)
- Using the Nernst equation to calculate equilibrium potentials
a. The Nernst equation is used to calculate the equilibrium potential at a given concentration difference of a permeable ion across a cell membrane. It tells us what potential would exactly balance the tendency for diffusion down the concentration gradient; in other words, at what potential would the ion be at electrochemical equilibrium?
E= -2.3 RT/zF log 10 Ci/Ce
E=equilibrium potential (mV)
2.3RT/F =constants (60 mV at 37C)
z=charge on the ion (+1 for Na+; +2 for Ca2+; -1 for Cl-)
Ci=intracellular concentration (mM)
Ce=extracellular concentration (mM)
b. Sample calculation with the Nernst equation
- If the intracellular (Na+) is 15 mM and the extracellular (Na+) is 150 mM, what is the equilibrium potential for Na+?
ENa+= -60mV/z log 10 Ci/Ce
= -60mV/+1 log 10 15mM/150mM
= -60mV log 10 0.1
=+60mV
Diffusion and equilibrium potentials (continued)
Approximate values for EP in nerve and muscle:
Know these
ENa+ +65mV
ECa2+ +120mV
EK+ -85mV
ECl- -85mV
Resting membrane potential
- is expressed as the measured potential difference across the cell membrane in millivolts (mV).
- is, by convention, expressed as the intracellular potential relative to the extracellular potential. Thus, a resting membrane potential of -70 mV means 70mV, cell negative.
Resting membrane potential – cell is in resting phase
no stimulus to cell membrane
inside the cell is negative and few K+ ions
outside of cell is full of positive charged ions(Na+)
-70mV
Action potential
A. Depolarization makes the membrane potential less negative (the cell interior becomes less negative).
B. Hyperpolarization makes the membrane potential more negative (the cell interior becomes more negative).
C. Inward current is the flow of positive charge into the cells. Inward current depolarizes the membrane potential.
D. Outward current is the flow of positive charge out of the cell. Outward current hyperpolarizes the membrane potential.
E. Action potential is a property of excitable cells (nerve, muscle) that consists of a rapid depolarization, or upstroke, followed by repolarization of the membrane potential. Action potentials have stereotypical size and shape, are propagating, and are all-or-none.
F. Threshold is the membrane potential at which the action potential is inevitable. Inward current depolarizes the membrane. If the inward current depolarizes the membrane to threshold, it produces an action potential. If the inward current is not sufficient to depolarize the membrane to threshold, it does not produce an action potential.
Ionic basis of the nerve action potential
Resting membrane potential
- is approximately -70mV, cell negative.
- is the rest of the high resting conductance to K+, which drives the membrane potential toward the K+ equilibrium potential.
- At rest, the Na+ channels are closed and Na+ conductance is low.
Ionic basis of the nerve action potential
Upstroke of the action potential
- Inward current depolarizes the membrane potential to threshold.
- Depolarization causes rapid opening of the activation gates of the Na+ channel, and the Na+ conductance of the membrane promptly increases.
- The Na+ conductance becomes higher than the K+ conductance, and the membrane potential is driven toward (but does not quit reach) the Na+ equilibrium potential of +65mV. Thus, the rapid depolaization during the upstroke is caused by an inward Na+ current.
- The overshoot is the brief portion at the peak of the action potential when membrane potential is positive.
- Tetrodotoxin (TTX) blocks these voltage-sensitive Na+ channels and abolishes action potentials
Know TTX
A stimulus to cell membrane shows a reaction from cell membrane moves from negative to positive only a few Na+ channels open **threshold** the slow opening of Na+ channels
After threshold fast opening of Na+ channels many Na+ ions enter cell **Depolarization** cell becomes saturated from Na+ ion \+65mV AKA = equilibrium potential for Na+ met
Ionic basis of the nerve action potential
Repolarization of the action potential
- Depolarization also closes the inactivation gates of the Na+ channel. Closure of the inactivation gates results in closure of the Na+ channels, and the Na+ conductance returns toward zero.
- Depolarization slowly opens K+ channels and increases K+ conductance to even higher levels than at rest.
- The combined effect of closing the Na+ channels and greater opening of the K+ channels makes the K+ conductance higher than the Na+ conductance, and the membrane potential is repolarized. Thus, repolarization is caused by an outward K+ current.
Repolarization
K+ leave cell as action potential decreases
Ionic basis of the nerve action potential (continued)
Absolute refractory period-is the period during which another action potential cannot be elicited, no matter how large the stimulus.
Relative refractory period
- begins at the end of the absolute refractory period and continues until the membrane potential returns to the resting level.
- An action potential can be elicited during this period only if a larger than usual inward current is provided.
Accommodation
-occurs when the cell membrane is held at a depolarized level such that the threshould potential is passed without firing an action potential. –is demonstrated in hyperkalemia, in which skeletal muscle membranes are depolarized by the high serum K+ concentration. Although the membrane potential is closer to threshold, action potentials do not occur because inactivation gates on Na+ channels are closed by depolarization, causing muscle weakness.
Absolute refractory period
cell membrane receives second stimulus during depolarization phase
the cell membrane cannot receive the second stimulus and cannot show any reaction
Relative refractory period
second stimulus is sent to cell membrane during repolarization
the cell membrane accepted and it shows reaction to that stimulus
Conduction velocity is increased by:
a. Increased fiber size. Increasing the diameter of a nerve fiber results in decreased internal resistance; thus, conduction velocity down the nerve is faster.
B. Myelination. Myelin acts as an insulator around nerve axons and increases conduction velocity. Myelinated nerves exhibit saltatory conduction because action potentials can be generated only at the nodes of Ranvier, where there are gaps in the myelin sheath.
The is a difference between myelinated and non myelinated
the myelinated has faster action potential and conduction velocity than non myelinated
The myelin sheath has a membrane
the nodes of Ranvier has gaps which makes the conduction velocity jump between membrane segments
must go faster
Saltatory conduction
Neuromuscular and synaptic transmission
General characteristics of chemical synapses
- An action potential in the presynaptic cell causes depolarization of the presynaptic terminal.
- As a result of the depolarization, Ca2+enters the presynaptic terminal, causing release of neurotransmitter into the synaptic cleft.
- Neurotransmitter diffuses across the synaptic cleft and combines with receptors on the postsynaptic cell membrane, causing a change in its permeability to ions and, consequently, a change in its membrane potential.
- Inhibitory neurotransmitters hyperpolarize the postsynaptic membrane; excitatory neurotransmitters depolarize the postsynaptic membrane.
Neuromuscular junction
- is the synapse between axons of motoneurons and skeletal muscle.
- The neurotransmitter released from the presynaptic terminal is Ach, and the postsynaptic membrane contains a nicotinic receptor.
- Synthesis and storage of Ach in the presynaptic terminal
- Choline acetyltransferase catalyzes the formation of Ach from acetyl coenzyme A (CaA) and choline in the presynaptic terminal.
- Ach is stored in synaptic vesicles with ATP and proteoglycan for later release. - Depolarization of the presynaptic terminal and Ca+ uptake
- Ca+ uptake causes release of Ach into the synaptic cleft
- Diffusion of Ach to the postsynaptic membrane and binding of Ach to nicotinic receptors.
- End plate potential (EPP) in the postsynaptic membrane
- Depolarization of adjacent muscle membrane to threshold
- Degradation of Ach (The EPP is transient because Ach is degraded to acetyl CoA and choline by acetylcholinesterase (AchE) on the muscle end plate.
- One-half of the choline is taken back into the presynaptic ending by Na+-choline cotransport and used to synthesize new Ach.
Ach inhibitors- neostigmine, and Hemicholinium blocks choline reuptake and depletes the presynaptic endings of Ach stores.
Disease-myasthenia gravis
- is caused by the presence of antibodies to the Ach receptors.
- is characterized by skeletal muscle weakness and fatigability resulting from a reduced number of Ach receptors on the muscle end plate.
- The size of the EPP is reduced; therefore, it is more difficult to depolarize the muscle membrane to threshold and to produce action potentials.
Treatment : AChE inhibitors.
Autoimmune disease
The antibody released blocks the Ach receptor and prevents binding of Ach to its receptor
Result: failure of post synaptic compartment function
Result: failure of muscle contraction
Sign/symptoms motor disorder sensory disorder in time can involve diaphragm muscle controls respiratory system and can cause death in severe conditions due to paralyzed diaphragm muscle
Neostigmine is an AChE inhibitor
prevents degradation of Ach
Achsterase inhibitor prevents effect of this enzyme and Ach is able to stay longer time in synaptic cleft and it can bind to unaffected receptor which leads to muscle contraction
Synaptic transmission
Types of transmission
a. One-to-one synapses –an action potential in the presynaptic element (the motor nerve) produces an action potential in the postsynaptic element (the muscle).
B. Many-to-one synapses-an action potential in a single presynaptic cell is sufficient to produce an action potential in the postsynaptic cell. Instead, many cells synapse on the postsynaptic cell to depolarize it to threshold. The presynaptic input may be excitatory or inhibitory.
Input to synapses
a. Excitatory postsynaptic potential (EPSP)
- are inputs that depolarize the postsynaptic cell, bringing it closer to threshold and closer to firing an action potential.
- are caused by opening of channels that are permeable to Na+ and K+, similar to Ach channels. Example ENT: include Ach, norepinephrine, epinephrine, dopamine, glutamate and serotonin.
b. Inhibitory postsynaptic potentials (IPSP)
are inputs that hyperpolarize the postsynaptic cell, moving it away from threshold and farther from firing and action potential.
-are caused by opening Cl- channels. Example: INT are gama-aminobutyric acid (GABA) and glycine.
Neurotransmitter
chemical substance which is secreted by cell body of neuron
some neurotransmitters act as stimulatory and others as inhibitory
most are stimulatory EXCEPT 2
GABA(gama-aminobutyric acid) and Glycine
Neurotransmitters
a. Ach
b. Norepinephrine, epinephrine, and dopamine
c. Seretonin
d. Histamine
e. Glutamate
f. GABAg.Glycine.
Neurotransmitters
Norepinephrine
is the primary transmitter released from postganglionic sympathetic neurons.
- is synthesized in the nerve terminal and released into the synapse to bind with alpha or beta receptors on the postsynaptic membrane.
- is removed from the synapse by reuptake or is metabolized in the presynaptic terminal by monoamine oxide (MAO) and catechol-O-methyltransferase (COMT).
The metabolites are: a. 3,4-Dihydroxymandelic acid (DOMA) b. Normetanephrine (NMN) 3-Methoxy-4-hydroxyphenylglycol (MOPEG) 3-Methoxy-4 hydroxymandelic acid, or vanillylmandelic acid (VMA)
*In pheochromocytoma, urinary excretion of VMA is increased.
Pheochromocytoma
when there is any tumor in adrenal medulla that leads to over secretion of adrenaline and noradrenaline
leads to severe hypertension
head aches, sleep disorders, nose bleeds, excess sweating, palpitations
treatment: remove tumor from adrenal medulla(center of adrenal gland)
Neurotransmitters
Epinephrine
- is synthesized from norepinephrine by the action of phenylethanolamine-N-methyltransferase.
- is secreted, along with norepinephrine, from the adrenal medulla.
Neurotransmitters
Dopamine
-is prominent in midbrain neurons.
-is released from the hypothalamus and inhibits prolactin secretion.
-is metabolized by MAO and COMT.
A. D1 receptors activate adenylate cyclase via a Gs protein.
B. D2 receptors inhibit adenylate cyclase via a Gi protein.
C. Parkinson’s disease involves degeneration of dopaminergic neurons that use the D2 receptors.
D. Schizophrenia involves increased levels of D2 receptors.
Schizophrenia
due to over secretion of Dopamine from brain stem
Parkinson’s disease
not enough dopamine
Deficiency of dopamine from hypothalamus leads to hyperprolactinemia
Neurotransmitters
Serotonin
- is present in high concentrations in the brain stem.
- is formed tryptophan.
- is converted to melatonin in the pineal gland.
Neurotransmitters
Histamine
- is formed from histidine.
- is present in the neurons of the hypothalamus.
Neurotransmitters
Glutamate
- is the most prevalent excitatory neurotransmitter in the brain.
- has a kainate receptor, which is an ion channel for Na+ and K+.
Neurotransmitters
GABA
- is an inhibitory neurotransmitter.
- is synthesized from glutamate by glutamate decarboxylase.
- has two types of receptors:
1. The GABAa receptor increases Cl- conductance and is the site of action of benzodiazepines and barbiturates.
2. The GABAb receptor increases K+ conductance.
Neurotransmitters
Glycine
- is an inhibitory neurotransmitter found primarily in the spinal cord and brain stem.
- increases Cl- conductance.
Water is the major constituent of the body and accounts for 65% to 75% of the total weight of an average adult.
Of this amount, two-third is contained within the body cells, or in the intracellular compartment; the remainder is contained in the extracellular compartment, a term that refers to the blood and tissue fluids.
Dissolved in this water are many :
- Organic molecules such as carbohydrates, lipids, proteins, and nucleic acids.
- Inorganic molecules and ions such as atoms.
ATOM
is the smallest particle still characterizing a chemical element.
cannot be cut into smaller particles, the atoms of modern parlance are composed of subatomic particles:
electrons
which have a negative charge, a size which is so small as to be currently unmeasurable.
protons
which have a positive charge, and are about 1836 times more massive than electrons.
neutrons
which have no charge, and are the same size as protons.
Protons and neutrons make up a dense, massive atomic nucleus, and are collectively called nucleons. The electrons form the much larger electron cloud surrounding the nucleus.
Atomic mass
The sum of the proton and neutrons in an atom is equal to the atomic mass of the atom
Atomic number
The number of protons in an atom is given as its atomic numberEX: Carbon has six protons and thus has an atomic number of 6.
Isotopes
Isotopes of an element have nuclei with the same number of protons (the same atomic number) but different numbers of neutrons.
Therefore, isotopes have different mass numbers, which give the total number of nucleons—the number of protons plus neutrons.
Chemical Bonding
Chemical compounds are formed by the joining of two or more atoms.
Covalent bond: bond in which one or more pairs of electrons are shared by two atoms.
Ionic bond: bond in which one or more electrons from one atom are removed and attached to another atom, resulting in positive and negative ions which attract each other.
Other types of bond include hydrogen bonding.
Acids
*Acids are ionic compounds ( a compound with a positive or negative charge) that break apart in water to form a hydrogen ion (H+).
*The strength of an acid is based on the concentration of H+ ions in the solution. The more H+ the stronger the acid.
Example: HCl (Hydrochloric acid) in water
Characteristics of Acids:
- *Acids taste sour
- *Acids react strongly with metals (Zn + HCl)
- *Strong Acids are dangerous and can burn your skin
Examples of Acids:1. Vinegar 2. Stomach Acid (HCl)3. Citrus Fruits
Bases
- Bases are ionic compounds that break apart to form a negatively charged hydroxide ion (OH-) in water.
- The strength of a base is determined by the concentration of Hydroxide ions (OH-). The greater the concentration of OH- ions the stronger the base.
Example: NaOH (Sodium Hydroxide-a strong base) in water
**Solutions containing bases are often called alkaline.
Characteristics of Bases: **Bases taste bitter **Bases feel slippery **Strong bases are very dangerous and can burn your skin Examples: 1. Sodium Hydroxide 2. Ammonia
Neutralization Reactions
** When acids and bases are added to each other they react to neutralize each other if an equal number of hydrogen and hydroxide ions are present.
When this reaction occurs -salt and water are formed.
HCl + NaOH = NaCl + H2O
(Acid) (Base)—(Salt) (Water)
pH Scale and Indicators
**The strength of an acid or base in a solution is measured on a scale called a pH scale.
**The pH scale is a measure of the hydrogen ion concentration. It spans from 0 to 14 with the middle point (pH 7) being neutral (neither acidic or basic).
Any pH number greater than 7 is considered a base and any pH number less than 7 is considered an acid. 0 is the strongest acid and 14 is the strongest base.
Buffers
A buffer is a system of molecules and ions that acts to prevent changes in H concentration and thus serves to stabilize the PH of a solution. In blood plasma, for example, the pH is stabilized by the following reversible reaction involving the bicarbonate ion (HCO3) and carbonic acid (H2CO3)
Blood pH
Lactic acid and other organic acids are produced by the cells of the body and secreted into blood. The arterial pH normally does not decrease but remains remarkably constant at pH 7.40-0.05.
Carbohydrates
Carbohydrates are the major source of energy for the body.
They are composed mostly of the elements carbon (C), hydrogen (H), and oxygen (O).
Carbohydrate Metabolism Disorders
Carbohydrates are the body’s sugar source. Sugars used to provide energy for the body include glucose , sucrose , fructose among many others. Some sugars need to be broken down, usually by enzymes , before they can be used by the body.
If the enzymes needed are not present (usually due to an inherited disorder), these sugars can build up and cause problems. The type of problem depends on the sugar involved.
Carbohydrate Metabolism Disorders:
Galactosemia
Galactosemia is an inherited autosomal recessive trait that affects the way the sugar galactose is broken down, due to the lack of the enzyme galactose-1-phosphate uridyl transferase.
Galactose can be found on its own in food or is the result of lactose (milk sugar) being broken down into galactose and glucose.
The body uses glucose for energy. In galactosemia, galactose then builds up and becomes toxic. In reaction to this build up of galactose the body makes some abnormal chemicals.
Clinical sign and symptoms The build up of galactose and the other chemicals can cause serious health problems:
- swollen and inflamed liver
- kidney failure
- ovarian failure in girls
- mental growth
- cataracts in the eyes
Treatment The treatment for galactosemia is to restrict galactose and lactose from the diet for life. ----- Galactose-1-phosphate uridyl transferase in large quantities hurts intestine
Symptoms
sever diarrhea
malabsorption in GI
accumulation in kidney, ovary, eye, liver, and CNS
Mental growth = retardation
Need to avoid things like milk
Functions of Proteins
- Binding, transport and storage - small molecules are often carried by proteins in the physiological setting (for example, the protein hemoglobin is responsible for the transport of oxygen to tissues). Many drug molecules are partially bound to serum albumins in the plasma.
- Molecular switching - conformational changes in response to pH or ligand binding can be used to control cellular processes .
- Coordinated motion - muscle is mostly protein, and muscle contraction is mediated by the sliding motion of two protein filaments, actin and myosin.
- Structural support - skin and bone are strengthened by the protein collagen.
- Immune protection - antibodies are protein structures that are responsible for reacting with specific foreign substances in the body.
- Generation and transmission of nerve impulses - some amino acids act as neurotransmitters, which transmit electrical signals from one nerve cell to another. In addition, receptors for neurotransmitters, drugs, etc. are protein in nature. An example of this is the acetylcholine receptor, which is a protein structure that is embedded in postsynaptic neurons.
- Control of growth and differentiation - proteins can be critical to the control of growth, cell differentiation and expression of DNA. For example, many hormones and growth factors that regulate cell function, such as insulin or thyroid stimulating hormone are proteins.
- ## if protein and caloric intake are both inadequate, a condition known as marasmus occurs. Marasmus presents with a stoppage of growth, extreme muscle loss, and weakness.Albumins main function is to control osmolarity in blood
prevents edema
Hormones
insulin, glucagon are protein based
Collagen is protein
Pigment cells are protein
Marasmus
Marasmus is a form of severe protein-energy malnutrition characterized by energy deficiency. Cachexia.
Clinical signs
The signs are common characteristics of protein-energy malnutrition:
-dry skin, loose skin folds hanging over the gluti, axillae, etc.
-Drastic loss of adipose tissue from normal areas of fat deposits like buttocks and thighs.
-The afflicted are often fretful, irritable, and voraciously hungry.
-There may be alternate bands of pigmented and depigmented hair (flag sign), or flaky paint appearance of skin due to peeling.
—-
(clinical point)Deficiency of protein leads to deficiency of immune system, protein hormones, pigment cells impacted, muscles atrophied, dryness of skin, severe diarrhea, imbalance of electrolytes(deficiency of ions), lose weight, weakness, malabsorption of digestion and nutrients
Metabolic disturbances:
Little or no water retention is present. Potassium and sodium depletion may occur if diarrhea persist. Serum protein levels are diminished. As general wasting occurs and metabolism approaches basal levels, the liver suffers acute and severe protein depletion and loss of its amino acid pool.
Treatment:
As in kwashiorkor, first correct the electrolyte imbalance followed by a gradual feeding program.
Protein replacement and electrolyte correction is needed for treatment
Lipids
Lipids, which consist of fats and oils, are high-energy yielding molecules composed mostly of carbon (C), hydrogen (H), and oxygen (O) (though lipids have a smaller number of oxygen molecules than carbohydrates have).
The important difference between saturated and unsaturated fatty acids
- is that saturated fatty acids are the most important factor that can increase a person’s cholesterol level. An increased cholesterol level may eventually result in the clogging of blood arteries and, ultimately, heart disease.
Not all fatty acids are considered harmful.
*In fact, certain unsaturated fatty acids are considered essential nutrients. Like the essential amino acids, these fatty acids are essential to a person’s diet because the body cannot produce them. The essential fatty acids serve many important functions in the body, including regulating blood pressure and helping to synthesize and repair vital cell parts.
Lipid disorder
The medical term for high blood cholesterol and triglycerides is lipid disorder. Such a disorder occurs when you have too many fatty substances in your blood.
These substances include cholesterol and triglycerides.
A lipid disorder increases your risk for atherosclerosis and heart disease.
Atherosclerosis
Atherosclerosis is a condition in which fatty material collects along the walls of arteries. This fatty material thickens, hardens, and may eventually block the arteries.
Causes, incidence, and risk factors
Atherosclerosis is a common disorder of the arteries. It occurs when fat, cholesterol, and other substances build up in the walls of arteries and form hard substances called plaque.
Eventually, the plaque deposits can make the artery narrow and less flexible. This makes it harder for blood to flow. If the coronary arteries become narrow, blood flow to the heart can slow down or stop, causing chest pain (stable angina), shortness of breath, heart attack, and other symptoms.
Atherosclerosis is obstruction or closure of blood vessels
Due to excess cholesterol(hypercholesterolemia) hyperlipidemia hypercalciumia more than 10mg/dL calcification of blood vessels fragile and rupture of BV
Atherosclerosis can cause
myocardial infraction
hypertension
Ketone bodies
are three water soluble compounds that are produced as by-products when fatty acids are broken down for energy. They are used as a source of energy in the heart and brain.
In the brain, they are a vital source in fasting.
The three ketone bodies are acetoacetate, beta-hydroxybutyrate and acetone, although beta-hydroxybutyrate is not technically a ketone but a carboxylic acid.
Ketone bodies
Uses in the heart and brain
Ketone bodies can also be used for energy. Ketone bodies are transported from the liver to other tissues, where acetoacetate and beta-hydroxybutyrate can be reconverted to acetyl-CoA to produce energy, via the Krebs cycle.
The heart gets much of its energy from ketone bodies, although it also uses a lot of fatty acids.
The brain gets its energy from ketone bodies when insufficient glucose is available (e.g. when fasting).
Ketosis and ketoacidosis
Any production of these compounds is called ketogenesis, and this is necessary in small amounts.
But, when excess ketone bodies accumulate, this abnormal (but not necessarily harmful) state is called ketosis.
When even larger amounts of ketone bodies accumulate such that the body’s pH is lowered to dangerously acidic levels, this state is called ketoacidosis.
Ketone Bodies:
What They Are, How They Accumulate
In some people with diabetes mellitus, the pancreas releases insufficient amounts of insulin or no insulin at all. Consequently, glucose goes largely undelivered.
In a desperate attempt to provide fuel, the body begins feeding on itself – that is, it breaks down muscle and fat to burn as fuel. Ketone bodies are a byproduct of this process.
Ketone bodies consist chemically of three substances (beta-hydroxybutyric acid, acetoacetic acid, and acetone).
When ketone bodies are released, they enter the bloodstream, acidify the blood, and are eventually excreted mostly in urine. (One type of ketone body exits via the lungs.) Without treatment, glucose and ketone bodies may build to dangerous levels in the blood. Stress and illness can increase the risk of glucose and ketone buildup.
When glucose and ketone bodies build to very high levels, the following conditions then exist:
- Hyperglycemia: too much sugar in the blood.
- Ketoacidosis: too many ketone bodies in the blood. 3. Ketonuria: accumulation of ketone bodies in the urine. When ketone is excreted, sodium is excreted along with it.
Symptoms and Treatment
Symptoms of glucose and ketone-body overload include:
- Thirst, frequent urination
- Dehydration
- Nausea, vomiting
- Heavy breathing
- Dilation of the pupils and confusion resulting from the toxic effects of ketone bodies and acid accumulation on the brain.
- A breath odor resembling the smell of fruit.
(One type of ketone body, acetone, is excreted through the lungs, causing the fruity smell.) This symptom-complex can progress to coma and death.
Treatment
with insulin and intravenous fluids can restore normal levels of blood sugar and end ketoacidosis and ketonuria.
—-
Type 2 diabetes
genetic disorder
insulin receptor becomes resistant to insulin hormone
the production of insulin is not impacted but it can not use the receptor
Signs and symptoms are similar to type 1
Treatment insulin replacement does not work exercise, diet help medicine: metformin decreases blood sugar
Phospholipids
Cholesterol is precursor to steroids
Steroids
In term of structure, steroids differ considerably from triglycerides or phospholipids, cholesterol is an important molecule in the body because it serves as the precursor for the steroid hormones produced by gonads and adrenal cortex.
Prostaglandins
A prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Prostaglandins are found in virtually all tissues and organs. ---- Prostaglandins are in all cells can be vasoconstrictor or vasodialator important for erections(vasodialator)
Prostaglandin E2
can cause inflammation in temperature center and fever
Prostaglandin relaxes the cervix of uterus during delivery in pregnant female
can use synthetic prostaglandin to help with dialation
Role of the prostaglandins
-cause constriction or dilatation in vascular smooth muscle cells
-sensitize spinal neurons to pain
-constrict smooth muscle
-regulate inflammatory mediation
-regulate calcium movement
-regulate hormone regulation
-control cell growth
—-
Prostaglandins are in all cells
can be vasoconstrictor or vasodialator
important for erections(vasodialator)
Prostaglandin E2
can cause inflammation in temperature center and fever
Prostaglandin relaxes the cervix of uterus during delivery in pregnant female
can use synthetic prostaglandin to help with dialation
Diffusion potential
Notes
The cell membrane contains ion channels
some channels are gated(open and close)
Action potential
when cell membrane receives stimulus from outside leads to opening of some ion channels such as sodium(Na+)
Na+ enters into cell then it leads to depolarization of that cell
the cell shows reaction to the stimulus(aka action potential)
Cystic Fibrosis Notes
Mutation to gene structure
CFTR function
in physiology condition
normally exist in cytoplasm controls Cl- expression from cell into lumen of organs
in pathologic condition(genetic disorder) the mutation to CFTR which makes it unable to control Cl-
excess expression of Cl- occurs
Vas deferns
testicular/gonadal artery which is direct branch of abdominal aorta
sympathetic and parasympathetic cremaster muscle for ejaculation of semen
spermatic cord passes through inguinal canal then travels/connected to testicle
can lead to obstruction of spermatic cord yielding infertility
Pancreas
leads to pancreatitis
can cause deficiency of pancreatic enzymes and endocrine dirorders
Gi tract
mucus can cause obstruction in GI and severe diarrhea due to malabsorption and digestion
can lead to protein deficiency
Treatment:
no exact treatment for Cystic fibrosis
inflammation can be controlled by cortisol(anti-inflammatory to control the inflammation)
Blood Osmolality Notes
After severe dehydration the blood becomes concentrated leading to stimulation of osmoreceptors located on the wall of large blood vessels
two cranial nerves take the information to CNS(hypothalamus)
CN 9 and CN 10
the central osmoreceptor is stimulated
the nuclei “supraoptic” and “paraventricular” in hypothalamus secrete ADH(antidiuretic hormone)
ADH released into blood stream
blood stream carries ADH to nephron of kidney for water retention
after binding of ADH to V2 receptor the tubule reapportion of fluid by capillary
Conclusion: ADH dilutes concentrated blood by fluid reabsorption(know this)
ADH inhibits dehydration
it decreases blood osmotic pressure by dilution of blood
Edema Notes
Edema = accumulation of fluid inside the cell or intrstitial space
Causes
deficiency of Albumin and other proteins
destruction of capillary
trauma/congenital
obstruction or closure of lympathetic system
congenitial/bacterial or viral infection/tumor blockage that leads to severe edema
pregnancy
hormone changes can yield severe edema due to fluid retention
renal disorder(kidney)
kidney cannot extract excess fluid as urine
(example) – having cis/infection in kidney
cardiovascular disorder and hypertension
Enzymes as Catalysts
Chemically, enzymes are a subclass of proteins. For example ribozymes function as enzymes in reactions involving remodeling of the RNA molecules themselves, and in the formation of a growing polypeptide in ribosomes.
Functionally, enzymes (and ribozymes) are biological catalysts.
A catalyst is a chemical that:
- increases the rate of a reaction
- is not itself changed at the end of the reaction
- does not change the nature of the reaction or its final result
In order for a given reaction to occur, the reactants must have sufficient energy. The amount of energy required for a reaction to proceed is called the activation energy.
Mechanism of Enzyme action
Enzymes are proteins that catalyze (i.e.accelerate) chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, the products. Almost all processes in a biological cell need enzymes in order to occur at significant rates.
Enzyme activity can be affected by other molecules:
-Inhibitors are molecules that decrease enzyme activity; Many drugs and poisons are enzyme inhibitors.
- Activators are molecules that increase activity.
- Activity is also affected by temperature, chemical environment (e.g. pH), and the concentration of substrate.
- Some enzymes are used commercially,
for example, in the synthesis of antibiotics.
Mechanism of Enzyme action
Lock and key” model
since enzymes are rather flexible structures, the active site is continually reshaped by interactions with the substrate as the substrate interacts with the enzyme.
As a result, the substrate does not simply bind to a rigid active site, the amino acid side chains which make up the active site are moulded into the precise positions that enable the enzyme to perform its catalytic function.
In some cases, such as glycosidases, the substrate molecule also changes shape slightly as it enters the active site.
The active site continues to change until the substrate is completely bound, at which point the final shape and charge is determined.
Effect of the temperature and pH for enzymes
An increase in temperature will increase the rate of non-enzyme-catalyzed reactions.
At temperature of 0 degree C the reaction rate is immeasurably slow. As the temperature is raised above 0 degree C the reaction rate increases, but only up to a point.
At a few degrees above body temperature (which is 37 degree C) the reaction rate reaches a plateau.
A similar relationship is observed when the rate of an enzymatic reaction is measured at different pH values.
Cofactors
Some enzymes do not need any additional components to show full activity. However, others require non-protein molecules to be bound for activity.
Cofactors can be inorganic (e.g., metal ions such as Ca+, Mg2+).
Some enzymes with a cofactor requirement do not have a properly shaped active site in the absence of the cofactor.
In these enzymes, the attachment of cofactors causes a conformational change in the protein that allow it to combine with its substrate.
Coenzymes
Coenzymes are organic molecules, derived from water soluble vitamins such as niacin and riboflavin, that are needed for the function of particular enzymes.
Coenzymes participate in enzyme-catalyzed reactions by transporting hydrogen atoms and small molecules from one enzyme to another.
such as riboflavin, thiamine and folic acid are water soluble vitamins, this is when these compounds cannot be made in the body and must be acquired from the diet.
Coupled reactions:
Oxidation-Reduction
When an atom or a molecule gains electrons, it is said to become reduced; when it loses electrons, it is said become oxidized. Reduction and oxidation are always coupled reactions: an atom or a molecule cannot become oxidized unless it donates electrons to another, which therefore becomes reduced.
The atom or molecule that donates electrons to another is a reducing agent, and the one that accept electrons from another is an oxidizing agent.
Notice that the term oxidation does not imply that oxygen participates in the reaction. This term is derived from the fact that oxygen has a great tendency to accept electrons, that is to act as a strong oxidizing agent. Oxygen acts as the final electron acceptor in a chain of oxidation-reduction reactions that provides energy for ATP production.
Oxidation-reduction reactions in cells often involve the transfer of hydrogen atoms rather than free electrons. Since a hydrogen atom contains one electron (and one proton in the nucleus), a molecule that loses hydrogen becomes oxidized, and one that gains hydrogen becomes reduced.
Metabolism
All of the reactions in the body that involve energy transformation are termed metabolism.
Metabolism is the complete set of chemical reactions that occur in living cells. These processes are the basis of life, allowing cells to grow and reproduce, maintain their structures, and respond to their environments.
The chemical reactions of metabolism are organized into metabolic pathways, in which one chemical is transformed into another by a sequence of enzymes.
Enzymes allow the regulation of metabolic pathways in response to changes in the cell’s environment or signals from other cells.
Catabolism
Catabolic reactions release energy, usually by the breakdown of larger organic molecules into smaller molecules.
The catabolic reactions that break down glucose, fatty acids, the amino acids serve as the primary sources of energy for the synthesis of ATP.
For example, this means that some of the chemical-bond energy in glucose is transferred to the chemical bond energy in ATP. Since energy transfers can never be 100% efficient, some of the chemical-bond energy from glucose is lost as heat.
Anabolism
Anabolic reactions require the input of energy and include the synthesis of large energy-storage molecules, including glycogen, fat, and protein.
Aerobic cell respiration
Aerobic respiration requires oxygen in order to generate energy (ATP). It is the preferred method of pyruvate breakdown from glycolysis and requires that pyruvate enter the mitochondrion to be fully oxidized by the Krebs cycle.
The product of this process is energy in the form of ATP (Adenosine Triphosphate), by substrate-level phosphorylation, NADH.
The energy transfer involves oxidation-reduction reactions. Oxidation of a molecule occurs when the molecule loses electrons. This must be coupled to the reduction of another atom or molecule, which accepts the electrons.
In the breakdown of glucose and other molecules for energy, some of electrons initially present in these molecules are transferred to intermediate carriers and then to a final electron acceptor.
When a molecule is completely broken down to carbon dioxide and water within an animal cell, the final electron acceptor is always an atom of oxygen.
Because of the involvement of oxygen, the metabolic pathway that converts molecules such as glucose or fatty acid to carbon dioxide and water (transferring some of the energy to ATP) is called aerobic cell respiration.
Glycolysis
Glycolysis is the metabolic pathway by which glucose-a six-carbon sugar is converted into to molecules of pyruvic acid,or pyruvate.
Each pyruvic acid molecule contains three carbons, three oxygens, and four hydrogens.
The number of carbon and oxygen atoms in one molecule of glucose-C6H12O6- can thus be accounted for in the two pyruvic acid molecules.
Since the two pyruvic acids together account for only eight hydrogens, however, it is clear that four hydrogen atoms are removed from the intermediates in glycolysis.
Each pair of these hydrogen atoms is used to reduce a molecule of NAD.
In this process, each pair of hydrogen atoms donates two electrons to NAD, thus reducing it.
Glycolysis Molecule Amounts
Starting from one glucose molecule, therefore, glycolysis results in the production of two molecules of NADH and two H+. The H+ will follow the NADH in subsequent reactions, so for simplicity we can refer to reduced NAD simply as NADH .
Glycolysis is exergonic, and a portion of the energy that is released is used to drive the endergonic reaction ADP+ Pi =ATP.At the end of the gycolytic pathway, there is a net gain of two ATP molecules per glucose molecule:
Glucose + 2NAD+2 ADP+ 2Pi= 2pyruvic acid +2 NADH+ 2ATP
*NAD is:
Nicotinamide adenine dinucleotide (NAD) is an important coenzyme found in cells. It plays key roles as a carrier of electrons in the transfer of reduction potential.
NADH is the reduced form of NAD+, and NAD+ is the oxidized form of NADH.
Lactic acid pathway and Anaerobic respiration
Without oxygen, pyruvate is not metabolized by cellular respiration but undergoes a process of fermentation.
The pyruvate is not transported into the mitochondrion, but remains in the cytoplasm, where it is converted to waste products that may be removed from the cell.
This serves the purpose of oxidizing the hydrogen carriers so that they can perform glycolysis again and removing the excess pyruvate. This waste product varies depending on the organism.
In skeletal muscles, the waste product is lactic acid. This type of fermentation is called lactic acid fermentation. In yeast, the waste products are ethanol and carbon dioxide. This type of fermentation is known as alcoholic or ethanol fermentation.
In order for glycolysis to continue, there must be adequate amounts of NAD available to accept hydrogen atoms. Therefore, the NADH produced in glycolysis must become oxidized by donating its electrons to another molecule.
When oxygen is not available in sufficient amounts, the NADH (H+) produced in glycolysis is oxidized in the cytoplasm by donating its electrons to pyruvic acid.
This results in the re-formation of NAD and the addition of two hydrogen atoms to pyruvic acid, which is thus reduced. This addition of two hydrogen atoms to pyruvic acid produces lactic acid.
The metabolic pathway by which glucose is converted to lactic acid is frequently referred to by physiologists as Anaerobic respiration.
Fermentation
Fermentation is a process of energy production in a cell under anaerobic conditions (with no oxygen required). In common usage fermentation is a type of anaerobic respiration, however a more strict definition exists which defines fermentation as respiration under anaerobic conditions with no external electron acceptor.
For example, even in the presence of abundant oxygen, yeast cells greatly prefer fermentation, as long as sugars are readily available for consumption.Sugars are the common substrate of fermentation, and typical examples of fermentation products are ethanol, lactic acid, and hydrogen.
However, more exotic compounds can be produced by fermentation, such as butyric acid and acetone.
Ischemia
refers to inadequate blood flow to an organ, such that the rate of oxygen delivery is insufficient to maintain aerobic respiration.
Inadequate blood flow to the heart, or myocardial ischemia, may occur if the coronary blood flow is occluded by atherosclerosis, a blood clot or by an artery spasm. It has severe pain in the chest and left arm area.
This pain is associated with increased blood levels of lactic acid which are produced by the ischemic heart muscle.
Glycogenesis
Glycogenesis is the formation of glycogen from glucose. Cells cannot accumulate very many separate glucose molecules, instead, many organs, particularly the liver, skeletal muscles, and heart, store carbohydrates in the form of glycogen.
In this process, glucose is converted to glucose 6-phosphate by utilizing the terminal phosphate group of ATP. Glucose 6-phosphate is then converted into its isomer, glucose 1-phosphate.
Finally, the enzyme glycogen synthase removes these phosphate groups as it polymerizes glucose to form glycogen.
Glycogenolysis
The enzyme glycogen phosphorylase catalyzes the breakdown of glycogen to glucose1-phosphate. The Glucose 1-phosphate is then converted to glucose 6-phosphate.
The conversion of glycogen to glucose 6-phosphate is called glycogenolysis.
Glycogenolysis
In liver
In glycogenolysis, glycogen stored in the liver and muscles, is converted first to glucose-1- phosphate and then into glucose-6-phosphate.
In most tissues, glucose 6-phosphate can then be respired for energy (through glycolysis) or used to resynthesize glycogen.
Only in the liver, can the glucose 6-phosphate also be used to produce free glucose for secretion into the blood.
The liver contains an enzyme as glucose 6-phosphatase that can remove the phosphate can then be transported through the cell membrane. The liver, then, can secrete glucose into the blood. Liver glycogen can thus supply blood glucose for use by other organs.
Glycogenolysis:
In skeletal muscles
Skeletal muscles, which have large amounts of glycogen, can generate glucose 6-phosphate for their own glycolytic needs, but they cannot secrete glucose into the blood because they lack the ability to remove the phosphate group.
Two hormones which control glycogenolysis are a peptide, glucagon from the pancreas and epinephrine from the adrenal glands.
Glucagon is released from the pancreas in response to low blood glucose and epinephrine is released in response to a threat or stress.
Both hormones act upon enzymes to stimulate glycogen phosphorylase to begin glycogenolysis and inhibit glycogen synthetase (to stop glycogenesis).
Gluconeogenesis
In human and other mammals, much of the lactic acid produced in anaerobic respiration is later eliminated by aerobic respiration of the lactic acid to carbon dioxide and water.
However, some of the lactic acid produced by exercising skeletal muscles is delivered by the blood to the liver. Within the liver cells under these conditions, the enzyme lactic acid dehydrogenase (LDH) converts lactic acid to pyruvic acid.
Un like most other organs, the liver contains the enzymes needed to take pyruvic acid molecules and convert them to glucose 6-phosphate, a process that is essentially the reverse of glycolysis.
Glucose 6-phosphate in liver cells can then be used as an intermediate for glycogen synthesis, or it can be converted to free glucose that is secreted into the blood.
The conversion of noncarbohydrate molecules (not just lactic acid but also amino acids and glycerol) through pyruvic acid to glucose is an extremely important process called gluconeogenesis.
Cori cycle
During exercise, some of the lactic acid produced by skeletal muscles may transformed through gluconeogenesis in the liver to blood glucose. This new glucose can serve as an energy source during exercise and can be used after exercise to help replenish the depleted muscle glycogen. Two-way traffic between skeletal muscles and the liver is called the Cori cycle. Through the Cori cycle, gluconeogenesis in the liver allows depleted skeletal muscle glycogen to be stored within 48 hours.
Kreb’s cycle
The aerobic respiration of glucose begins with glycolysis. Glycolysis results in the production of two molecules of pyruvic acid, two ATP, and two NADH+H+ per glucose molecule.
In aerobic respiration, pyruvic acid leaves the cell cytoplasm and enters the interior of mitochondria. Once pyruvic acid is inside a mitochondrion, carbon dioxide is enzymatically removed from each three-carbon-long pyruvic acid to form a two-carbon-long organic acid-acetic acid. The enzyme that catalyzes their reaction combines the acetic acid with a coenzyme called coenzyme A. The combination thus produced is called acetyl coenzyme A (acetyl CoA).
Glycolysis converts one glucose molecule into two molecules of pyruvic acid. Since each pyruvic acid molecule is converted into one molecule of acetyl CoA and one CO2, two molecules of acetyl CoA and two molecules of CO2are derived from each glucose. These acetyl CoA molecules serve as substrates for mitochondrial enzymes in the aerobic pathway, while the carbon dioxide is a waste product that is carried by the blood to lungs for elimination.
Once acetyl CoA has been formed, the acetic acid (two carbon long) combines with oxaloacetic acid ( four carbons long) to form a molecule of citric acid (six carbons long).Coenzyme A acts only as a transporter of acetic acid from one enzyme to another. The formation of citric acid begins a cyclic metabolic pathway known as the citric acid cycle, this cyclic pathway is called the Krebs cycle.
Kreb’s cycle
In this process, these events occur:
Through a series of reactions involving the elimination of two carbons and four oxygens (as two CO2 molecules) and the removal of hydrogens, citric acid is eventually converted to oxaloacetic acid, which completes the cyclic metabolic pathway.
In this process, these events occur:
1. One guanosine triphosphate (GTP) is produced which donates a phosphate group to ADP to produce one ATP.
2. Three molecules of NAD are reduced to NADH
3. One molecules of FAD is reduced to FADH2.
*NAD:Nicotinamide adenine dinucleotide (NAD) is an important coenzyme found in cells. It plays key roles as a carrier of electrons in the transfer of reduction potential.
NADH is the reduced form of NAD+, and NAD+ is the oxidized form of NADH.
*(flavin adenine dinucleotide (FAD) is the precursor molecule to FADH2. Upon bonding to two hydrogen atoms, FAD is then changed to FADH2 and is turned into an energy-carrying molecule).
The production of NADH and FADH2 by each turn of the Krebs cycle is far more significant, in terms of energy production, than the single GTP (converted to ATP) produced directly by the cycle. This is NADH and FADH2 eventually donate their electrons to an energy-transferring process that results in the formation of large number of ATP.
In summary, the Kreb’s cycle removes carbon dioxide molecules from glucose in a stepwise fashion to release energy.
Mitochondria
Structure
Mitochondria vary considerably in shape and size, but all have the same basic architecture.
There is a smooth outer membrane, surrounding a very convoluted inner membrane. The convolutions form recognizable structures called cristae. The two membranes have very different properties.
Together they create two compartments, namely the intermembrane space (the comparment between the membranes), and the matrix (the very interior of the mitochondria).
Electron transport
In the cristae of inner mitochondrial membrane are a series of molecules that serve as an electron-transport system during aerobic respiration.Components of the electron transport system include complexes I, II, III, and IV, plus two individual molecules, coenzyme Q and cytochrome c.
The Electron Transport Chain
The ETC is a series of electron acceptors and proton pumps in the membranes of mitochondrial cristae that accept the high energy electrons from NADH and FADH2. As the electrons pass through the ETC, their energy is used to pump protons(H+) from the matrix to the outer compartment. These protons will later diffuse back to the matrix and their energy is used to make 32 ATP.
Makes 32 ATP.
Review picture slide
Chemiosmosis
is the process where protons diffuse from the outer compartment (high concentration) through ATP Synthase in the Cristae to the Matrix (low H+ Concentration). The energy in the protons as they pass is used by ATP synthase to create 32 ATP.
Review picture slide
Electron Transport / Oxidative Phosphorylation
The purpose of the Electron Transport Chain is to receive the high energy electrons carried by the coenzymes NADH &FADH2 and use the energy from these electrons to pump protons out of the matrix. A high concentration of protons results. As the protons diffuse back to the matrix, their energy is used by the ATP synthase to create ATP.
Electron Transport:
a) Occurs at cristae (Inner membranes)
b) NADH & FADH2 deliver H+ and e- to cristae.
c) Electrons “transport” along cristae through electron acceptors, provide energy to pump H+ from matrix to outer compartment.
d) Concentration of H+ is now higher in outer compartment. H+ pass through ATP synthases in cristae back to matrix. ATP are made. This is known as chemiosmosis.
e) Last step involves H+ & e- added to oxygen. This frees NAD+ to return to glycolysis & Krebs Cycle to pick up more H+ & e-.
Breakdown of fat (lipolysis)
When fat stored in adipose tissue is going to be used as an energy source, lipase, enzymes hydrolyze triglycerides into glycerol and free fatty acids in a process called lipolysis.
These molecules serve as blood-borne energy carriers that can be used the liver, skeletal muscles, and other organs for aerobic respiration.
Most fatty acids consist of a long hydrocarbon chain with a carboxyl, or carboxylic acid group (COOH) at one end. In a process known as B-oxidation enzymes remove two-carbon acetic acid molecules from the acid end of a fatty acid chain.
Cystic Fibrosis and Organs
Mutation to gene structure
CFTR function
in physiology condition
normally exist in cytoplasm controls Cl- expression from cell into lumen of organs
in pathologic condition(genetic disorder) the mutation to CFTR which makes it unable to control Cl-
excess expression of Cl- occurs
Vas deferns
testicular/gonadal artery which is direct branch of abdominal aorta
sympathetic and parasympathetic cremaster muscle for ejaculation of semen
spermatic cord passes through inguinal canal then travels/connected to testicle
can lead to obstruction of spermatic cord yielding infertility
Pancreas
leads to pancreatitis
can cause deficiency of pancreatic enzymes and endocrine disorders
Gi tract
mucus can cause obstruction in GI and severe diarrhea due to malabsorption and digestion
can lead to protein deficiency
Treatment:
no exact treatment for Cystic fibrosis
inflammation can be controlled by cortisol(anti-inflammatory to control the inflammation)
Edema Causes
Edema = accumulation of fluid inside the cell or intrstitial space
Causes
deficiency of Albumin and other proteins
destruction of capillary
trauma/congenital
obstruction or closure of lympathetic system
congenitial/bacterial or viral infection/tumor blockage that leads to severe edema
pregnancy
hormone changes can yield severe edema due to fluid retention
renal disorder(kidney)
kidney cannot extract excess fluid as urine
(example) – having cis/infection in kidney
cardiovascular disorder and hypertension
Neurotransmitters
Ach
stimulatory neurotransmitter
secreted by neuron
important role in neuromuscular junction and muscle contraction
important neurotransmitter for autonomic nervous system which controls internal organs(heart, digestive, etc)
main nerve of parasympathetic
CN 10(Vagus nerve)
releases Ach which decreases the heart rate and increases motility/movement of GI
(Clinical Point) over secretion of Ach in GI tract can cause inflammation of GI such as gastritis
Neurotransmitters
Norepinephrine
important neurotransmitter for sympathetic nervous system
controls blood pressure, heart rate, heart function, relaxes smooth muscle/bronchi, stimulates sweat glands
Norepinephrine and epinephrine are secreted by adrenal medulla(central part of adrenal gland located above kidney)
either as hormone or neurotransmitter the function are similar
Neurotransmitters
Epinephrine
involved in blood pressure and heart
controls blood glucose by stimulation of liver
Neurotransmitters
Dopamine
the effect of dopamine depends on location of production
secreted by black substance in brain stem
controls movement
deficiency causes Parkinsons disease
Excess leads to Schizophrenia
secreted by prefrontal love of brain
controls problem solving, social behavior
deficiency leads to problem solving disorder and social behavior disorder
secreted by hypothalamus
inhibits prolactin secretion
prolactin stimulates mammary gland for breast feeding(increases during pregnancy)
most important factor
controls sexual behavior in male
deficiency leads to hyperprolactinenima
too much prolactin in blood
prolactin can suppress male hormone and lead to infertility in male
prolactin in pregnant female suppresses female sex hormones which inhibits menstruation and ovulation
(clinical point) degreased prolactin in pregnant female leads to abortion
decrease prolactin increases sex hormons = mensuration
Medicine: Bromocriptine decreases prolactin level which is synthetic dopamine
stress increases prolactin in nonpregnant females which suppresses ability to have children
Bromocriptine can decrease prolactin and make woman fertile again
Neurotransmitters
Seretonin
act as neutransmitter or neurohormone secreted by neurons controls mood, appetite, sleep deficiency leads to depression or bipolar disorders sunlight stimulates serotonin for depression sunlight therapy is good serotonin replacement secact as neutransmitter or neurohormone secreted by neurons controls mood, appetite, sleep deficiency leads to depression or bipolar disorders sunlight stimulates serotonin for depression sunlight therapy is good serotonin replacement reted by GI tract, especially from stomach which controls the gastric acid secretion
Neurotransmitters
Histamine
function depends on location of production
secreted by neuron and mast cells
mast cells that secrete histamine act as vasodialator in skin
vaso and broncho constrictor in respiratory system
(clinical point) histamine levels increases in asthmatic patients which is why they have inflammation of bronchi
effect of histamine in GI increases HCl secretion
HCl converts pepsinogen to pepsin for digestion of proteins
high histamine can lead to gastritis or gastric ulcer
blocking histamine receptor used to decrease histamine effect
treatment of gastritis
histamine level increases to allergic reaction
causes inflammation
Neurotransmitters
Glutamate
stimulatory neurotransmitter which controls memory learning and sodium potassium channels
Neurotransmitters
GABA and Glycine
Gama amino butyric acid(GABA)
the only 2 inhibitory neurotransmitters on list
both stimulate the Cl- channels and opens the channels for chloride to enter cells
Ketone Bodies Class Notes and Clinical points
Including Type 1 diabetes
3 acids form ketone bodies
acetone
beta-hydroxybutyrate
acetoacetate
Ketones are the product of fatty acids being broken down
Over secretion of ketones means the acid level drops and is not good for brain
(clinical point)
when acid level is high the CO 2 level is
not good for brain
the neuron requires oxygen molecules not CO2 molecules
can lead to ketoacidosis and patient can go into coma
The relationship between type 1 diabetes and ketones
(clinical point)
type 1 is an autoimmune disease
the antibodies such as IGG attaches to beta cells of pancreas(cells secrete insulin)
deficiency of insulin = deficiency of glucose inside the cell
leads to failure of ATP production
leads to hyperglycemia(over 120mm in BV)
hyperglycemia can cause vasculopathy because vasculopathy means excess sugars can destroy the endothelial of blood vessels which leads to hypoxemia(BV can not carry enough oxygen molecules to cells)
vasculopathy can happen in any blood vessels(heart, brain, kidney, renal artery, eye) and possibly rupture the blood vessels
neuropathy can be peripheral or central
no glucose then the neurons are starving due to deficiency of glucose
central neuropathy(for example optic nerve)
untreated type 1 diabetes can cause blindness due to this
excess glucose can cause glucourea(more than 300-350mg/dL)
sodium channels are saturated and can not transport glucose any longer.
leads to glucose in urine
glucose in urine increases osmotic pressure
leads to absorb more fluid in urine(in nephron) then patient has polyurea(need to go all the time/frequently)
frequent urination lead to polydipsia(thirsty)
excess glucose in renal artery leads to hypertension because renal artery cannot carry large amount of blood to renal artery
fluid gets into nephron/kidney then backflow(hypertension)
risk for renal failure increases and impacts heart function
All the above leads to body breaking down fatty acids and using ketones but this leads to ketourea ketoacidosis(or hyperglycemic coma)
Treatment
insulin replacement
oral will not work because pepsin in stomach can break down insulin
use IV or subdermal
Coenzymes carry ions such as
hydrogen ion from cytoplasm to mitochondria
Reduction – gaining electrons
Oxidation – loses electron
Reduction – gaining electrons
Oxidation – loses electron
During cell respiration the cell uptakes
glucose from blood which is under control of insulin. The target cell uptakes the glucose and it breaks down into small pieces. This small pieces are used for the production of ATP by mitochondria. For ATP production the cell uses(the last molecule in chain) is oxygen and release CO2.
During cell respiration we have aerobic and anaerobic processes.
aerobic – cell receive sufficient oxygen molecules and produces ATP by mitochondria
anaerobic – there is not sufficient oxygen for cells to utilize. Cell in unable to produce ATP. Instead the cell converts the products of glucose into lactic acid
(Clinical point)
in some disorders when the cell has deficiency of oxygen then that cell can not produce ATP then P.A. is converted into Lactic acid which remains in the cytoplasm
- failure of ATP production in that cell
myocardial infarction blood test shows lactic acid levels are high because of cell death of myocardium due to insufficiency of blood supply(oxygen supply) to myocardial tissue
this is a positive sign for myocardial infarction
sometimes physiological condition that lactic acid level increases
for example, going to the gym causes pain in muscles because the body can not supply muscles enough oxygen for aerobic respiration
lactic level increases because of deficiency of oxygen supply to muscle tissue
Ischemia
Any obstruction of a blood vessel can cause this
Blood vessels to heart become obstructed the muscle tissue can not receive oxygen
Glycogenesis occurs in
Liver and skeletal muscle
Glycogenolysis
Liver VS Skeletal production
Liver production is shared to other organs because the liver has enzyme glucose 6-phosphatase to remove the phosphate and transported through cell membrane to blood supply.
Skeletal muscle production does not have the enzyme and cannot transport the glucose to the blood supply. Stays within the skeletal muscle.
Cori cycle AKA gluconeogensis
After releasing of lactic acid by muscles then lactic acid gets into Liver. Liver converts lactic acid into pyruvic acid then glucose. Then liver releases the glucose into blood stream and blood stream carries new glucose to muscle again. Muscle uptakes glucose for production of ATP.
Krebs Cycle Location
Occurs in mitochondria
Uptakes the pyruvic acid from glucose then some other acids which are involved in Krebs cycle
The goal of Krebs cycle is to release CO2 and H2O
meanwhile it uptakes oxygen molecule for production of ATP
2 coenzymes, NAD and FAD, carry hydrogen ion and electron to mitochondria for production of ATP
Electron Transport Chain and Chemiosmosis
Hydrogen ion must pass through a channel
red – ATP synthase channel to come back into matrix
FAD and NAD are reduced with electron and hydrogen ion. They carry them to matric part of mitochondria
FAD and NAD are reduced with electron and hydrogen ion. They carry them to matric part of mitochondria. The coenzymes release the electrons which pass through electron transport chain of critae membrane. Because of this then hydrogen is released from coenzyme and is able to pass through cristae membrane and it gets to the outer compartment. After a while the concentration of hydrogen ion increases(chemiosmosis). Then hydrogen ion is able to move from higher concentrated to lower concentrated area in the matrix through the ATP synthase channel. Then the mitochondria uses the hydrogen ion with oxygen molecule to release H2O meanwhile ADP + P yields ATP
Breakdown of fat(lipolysis) notes
Breakdown to ketone bodies
Newborn bodies have brown fat
good source of ATP
Brain and muscle uptakes glucose which is good source of energy
