Cell Bio and Respiratory

The study of normal bodily structures

the study of physical changes in diseased bodily structures/tissues

the study of the function of normal organs and how they work together

• The study of the function in diseased/altered structures
• physiology under abnormal conditions of disease
• molecular alterations that cause the disease
• understanding of these alterations can be applied to healthcare and pt management

the cause or causes of a disease

the steps and patterning of a disease process

• rapid onset
• signs/sx develop quickly
• usually of short duration

an abnormality involving a tissue or organ due to a disease or injury

• local: confined to an area of the body
• systemic: distributed throughout the body (usually after gaining access to blood or lymph)
• WITHIN AN ORGAN DAMAGE CAN BE...
• Focal: one or more distinct sites of damage
• Diffuse: Damage spread throughout the organ

• subjective
• described by the patient
• effects of a disease that are reported by the patient
• ie: i have a cough is symptom, but if you see them coughing thats a sign

• you observe and measure them
• observable measurable trait
• ie lab values

• identification of disease or disease process
• using markers (physical chemical or biological markers) to identify
• can also use tests

• assessment of the outcome of a disease process
• what will happen to patient with a disease

• treatment for a disease
• either to cure or treat signs and symptoms

• conditions resulting from a prior disease
• ie someone has bronchitis in the past, there could be sequelae of pneumonia

• longer duration
• onset may be sudden or insidious
• usually take longer to develop
• or develop insidiously when you dont know about it and then seems to develop suddenly

• loss or alteration of homeostasis
• physical or mental capabilities cannot be fully utilized due to altered homeostasis which negatively affects our ability to function

normal physiological function and normal range of values that our body holds in place

• a characteristic combination of signs and symptoms associated with a particular disease
• ie syndrom of inappropriate secretion of antidiuretic hormone (SIADH)- diagnosed by a collection of signs and symptoms

• when you look at a disease you want to know what caused it
• genetic
• congenital
• acquired
• idiopathic
• iatrogenic
• nosocomial

genes responsible for a structural or functional defect

• genetic information is intact, but the intrauterine environment interferes with normal development
• happens because of alterations to the fetus in the uterus (ie fetus gets infection or exposed to an environmental toxin in utero)

• disease is caused by factors encountered after birth
• ie infections, environment etc

• cause is unknown
• but you still have to know the pathophysiology

medication induced

hospital acquired/induced

• our body is made up of cells
• they are the basic unit of function and life

cells can: replicate, do metabolism, respond to external stimuli, do locomotion, differentiate, and more

• interstitial fluid: the extra cellular fluid outside cells between them
• cytoplasm: intracellular fluid

• made up mostly of phospholipids in the bilayer
• also has cholesterol and proteins, some with channels/pumps and glycolipids or glycocalyx

• its a bilayer with hydrophillic heads facing in and outside the cell and hydrophobic tails facing eachother inside the membrane
• there are diff types of phospholipds depending on what type of head group and or what type of fatty acid is present in the phospholipid

• a phospholipid with an unsaturated fatty acid 
• this will allow the membrane to be more fluid

• it is selectively permeable to ions and organic molecules
• controls the movement of substances in and out of the cell

• integral
• peripheral
• receptor
• carrier
• channel
• anchoring
• enzymes

• lipids: phospholipid bilayer and cholesterols
• proteins: integral, peripheral, receptor, carrier, channel, anchoring, enzymes
• carbohydrates: glycolipids and glycoproteins

• diffusion
• active transport
• passive transport

• proteins that run across the cell membrane
• a transmembrane protein- its attached to the membrane

• proteins stuck on the inside or outside of the cell membrane
• on either the outer or inner leaf of the bilayer
• some can be easily removed from the membrane

• can recognize cells
• mainly for bacteria, viruses, hormones

• transport large molecules across the membrane in and out of the cell
• ie of molecules transported glucose, amino acids 
• example of a carrier protein: glucose carrier protein

• transport ions such as calcium, sodium and potassium in and out of the cell
• ie sodium channel

• biological catalysts
• a lot of enzymes are membrane bound, but some are free in the cell
• catalyze chemical reactions

• cytoskeletal proteins
• they anchor other proteins

• contains the fluid of the cell (cytosol)
• contains the organelles in the cytosol

• the fluid inside the cell
• aka intracellular fluid
• water with high potassium,low sodium and low chloride compared to the exctracellular fluid

small organs with independent functions and help give a cell its various characteristics to be the basic unit of life and function

• nonmembranous
• membranous

• they have functions, but arent bound by a membrane
• cytoskeleton, microvilli, centrioles, cillis, ribosomes, proteasomes

• aka membrane bound
• either are membrane bound or are membranes by themselves
• E.R. (rough and smooth), golgi, lysosomes, peroxisomes, mitochondria

needed for degredation of unwanted proteins in the cell

• have detoxifying enzymes in them making them capable of detoxification
• also have enzymes for lipid processng

important for protein synthesis

important for synthesis of lipids and sugars

• responsible for shipping material and for adding sugars to proteins
• collects the material that is synthesized and adds a label to it so the material can be sent to the proper desitnation

• bags of digestive enzymes at a very low pH
• they will digest almost anything

• inside: high potassium, low sodium, low chloride
• outside: low potassium, high sodium, high chloride
• this difference in ionic composition allows for the generation of resting potential and provides the substrates for generating electrical activity of the cell

the electrical potential of a neuron or other excitable cell relative to its surroundings when not stimulated or involved in passage of an impulse

• there will be reprecussions with water movement and consequentially in the cells life
• presence of ions in the right place is also important for maintenance of cell integrity and moving water across the membrane

• a double membrane organelle
• central cavity filled with matrix
• home to the electron transport chain enzymes and krebs cycle enzymes which allow the mitochondria to generate ATP

• inner membrane of the mitochondria folds into these cristae
• folding creates a large surface areas for chemical reactions of cellular respiration

what the central cavity of the mitochondria is filled with

• generation of ATP molecules which are used for running various chemical rxns of the cell
• powerhouse of the cell

• mitochondria self-replicate
• they increase with the need for ATP
• they have a circular DNA- mitochondrial DNA

37

• your mother
• because: during fertilization the sperm's mitochondria is in its mid piece which does not enter the egg in fertilization
• this is how people have been able to trace mitochondrial DNA all the way back to the african eve

• woman from whom all humans descended
• mitochondrial DNA has been traced back generations to find her

• structure in the cell with a double cell membrane called the nuclear envelope
• center of cellular operations

a profile of all chromosomes in a picuture

• surrounds nucleus
• has nuclear pores that allow material to get in and out of the nucleus

the space between the 2 nuclear membranes

• allow the nucleus to communicate with the cytoplasm
• allow material to get in and out of nucleus from cytoplasm

• a supportive nuclear matrix
• one or more nucleoli
• chromosomes

• DNA bound to proteins called histones
• individual ones are visible at metaphase- this is where a karyotype is made and you can count them by halting it at metaphase

bc it contains chromosomes that control and regulate cellular activity

• the meshwork visible in a resting cell
• when the cell is not dividing, the chromosomes are not discernable- you cant see the individual ones

• ppl used to think histones were the inherited material but its the DNA
• histones and DNA are the 2 components of chromosomes

• first its a double helix
• that dna is wound around histones and then condensed into chromatin fibers which is further condensed into the chromosome

• 2 chromatids, each with a p (short) arm and a q (long) arm
• centromere joining the 2 chromatids

there are both nonsex determining and sex determining chromosomes in the cell

non-sex determining chromosomes

sex determining chromosomes

• 2N aka diploid cells
• the cells of most of the body except the sex cells
• female: 22 pairs of autosomes and one pair of x
• male: 22 pairs of autosomes and one x and one y

• ova and sperm 
• 1N aka haploid cells
• ova: 22 single autosomes and one x (all ova are similar)
• sperms: 22 single autosomes and one x OR 1 y

arranged and numbered by length, longest first and shortest last

each chromosome also has its own banding pattern, and now bands that show with staining is how we classify them, but they are still organized by length

x inactivation

• occurs in the fetus
• a random phenomenon
• the maternal (m) and paternal (p) X chromosomes are both active in the zygote and in early embryonic cells
• one of them is silenced (randomly) early on in fetal development so in the adult female there is only 1 x chromosome working while the other one is inactive

• NO! 
• early in development, the first cells randomly inactivate and x and when they replicate and differentiate that continues so for the most part with a few exceptions, all organs have the same x inactivated, but different organs can have different inactivated x's

the female is an x-chromosome mosaic, meaning some of her cells have an inactive paternal X, while others have an inactive maternal x chromosome

it shrinks and becomes a little darkspot in the cell called the barr body

• Mary Lyons
• in 1960s

a molecule or structures made up of multiple monomers

• polymers of nucleotides
• the nucleotides are the monomers

• a monomer
• a molecule made up of 3 pieces: base + sugar + phosphate

• nucleotides joined together by their phosphates 
• aka: nucleic acid

• deoxyribose nucleic acid 
• has a deoxyribose pentose sugar
• adenine
• cytosine
• thymine
• guanine

• ribonucleic acid
• has a ribose pentose sugar
• adenine
• guanine
• cytosine
• uracil

nitrogen

• hydrogen bonds
• high temps ~90C
• as solution cools chains will come back together

• a will always bind t or u
• g will always bind c

• the one directional informational flow from DNA to protein
• DNA can replicate itself using DNA Polymerase
• DNA is transcribed into mRNA by RNA Pol which is translated into protien by ribosomes and tRNA

• a sequence of 3 dna bases
• dna is in triplets

all the triplets needed to code for a specific polypeptide

• Messenger: contains message from the gene
• Transfer: fetches amino acids for ribosomes in translation
• ribosomal: in ribosomes

• the cell membrane allows some molecules through but not others
• the membrane is made up mostly of lipids so lipids can easily travel across
• larger and/or charged mollecules have a more difficult time getting across

• a type of diffusion
• either simple of facilitated
• simple: same as diffusion
• facilitated: usually requires protein helpers

• movement of small molecules across cell membrane based on concentration gradient
• move from high [] to low [] 
• passive process

• uses ATP and works indepented of gradietn
• uses ion pumps and co-transport proteins
• ie- sodium/potassium pump
• transporters can be linked ie a glucose transport linked to a sodium transport

movement of water across the membrane based on the [] of ions

usually uses a transport or carrier protein

• k brought in and na pumped out
• this needs ATP and will shut down without it

• ion pumps
• secondary active transport (aka co transport)

direction of transport is the same for the driving molecule and driven molecule

• the sum of all the chemical reactions that occur in the body
• run by enzymes 
• you take large molecules and make them smaller or small molecules and make them larger and you are either synthesizing or using energy in the process

• synthesis of molecules
• requires input of energy
• ie- glucose to glycogen

• breakdwon of molecules
• releases energy
• degrade material in the cell for energy for the cell to use to function
• ie phospholipid into fatty acids

anabolism  + catabolism = metabolism

3

• breakdown of complex nutrients in the digestive tract
• happens outside the cell
• we take in food and digest it in the GI tract after digestion its absorbed
• ie food into protein, polysaccharides, or fat then those into amino acids, simple sugars, or fatty acids

• glycolysis, starts after material is absorbed
• occurs in the cytosol in the cytoplasm
• produces 2 atp molecules per 1 molecule glucose
• intracellular breakdown of the monomers to acytl coA accompanied by production of limited ATP and NADH

• kreb cycle and oxidative phosphorilation
• occurs in mitochondria
• production of NADH yeilding ATP via the electron transport chain, waste products are h2o, co2 nh3 and urea
• yeilds 36 atp

• use of oxygen in krebs and way more ATP produced
• without oxygen phase III is shut down and you only have II

once glucose is inside the cell, glycolysis occurs in the cytoplasm which results in pyruvic acid. This can either be made in to 2 ATP by anaerobic respiration and 2 lactic acid (phase II) or for the krebs cycle and ETC to make 38 ATP in aerobic respiration if oxygen is present

if the mitochondria is somehow compromised OR you have no oxygen

• acetyl coenzyme A
• a product of pyruvic acid metabolism
• this is used in the krebs cyle to make ATP

• not a lot of it
• so extra glucose will be converted to fat and glycogen by glycogenesis and lipogenesis

• glucose
• some other organs can potentially use fatty acids to conserve glucose for the brain
• if no glucose, brain function is compromised

• yes
• fat, amino acids, and carbs enter krebs cycle via Acetyl CoA
• although carbs are the main source of energy, fat can be broken down into ketone bodies which can be used for energy
• and proteins can be broken down into amino acids for energy

• brain: glucose, ketone bodies
• resting skeltal muscles:fatty acids, glucose, ketone bodies
• liver: fatty acids, ketone bodies, lactic acid
• heart: fatty acids, glucose, ketone bodies, lactic acid

• made from glucose, fat and amino acids
• can be used to synthesize steroids (ie hormones), fat (if you eat too much glucose), ketone bodies, atp (via krebs and etc)
• linked to hemaglobin and amino acid metabolsim
• makes water and co2 as by products

• when we eat proteins they are broken down into aas which are absorbed by cells and used to make more proteins for various things
• needed for growth and repair

• essential: 9 of them, you cant make them yourself, you have to get them from diet
• non essential: you still need them, but the body can make them. 11 of these

• Tryptophan
• Thronine
• Lysine
• Leucine
• Isoleucine
• Methionine
• Phenylalanine
• Histadine
• Valine

the process and steps a cell must go through in a sequential order to allow the cell to undergo cell division

• nuclear division: mitosis (somatic) or meiosis (reproductive)
• cytoplasmic division: cytokinesis

• G0
• G1
• S
• G2
• M

• g1, s, g2 phases
• this is the longest period of the cycle where the cell is preparing for mitosis

enzymes that are regulated by proteins called cyclins

proteins that accumulate in each phase and once they accumulate to a certain level they will activate cyclin independent kinase and the cell will transition to the next stage

• aka gates
• there are checkpoints throughout interphase with cycle independent kinases
• checkpoints are regulated by both cyclin proteins and cyclin dependent kinases

• no cyclins: cells cannot get past the checkpoint and cell cycle arrests
• too many: uncontrolled cell division. cancer cells have MANY cyclins

• no!
• ie brain cells dont

• the type of cell
• size of cell
• cell senescence
• levels of cylin and cyclin dependent kinase
• homeostasis
• apoptosis
• hormones and growth factors
• contact inhibition

• not all cells do it and they do at different rates
• liver cells dont divide normally, but CAN if theres an injury for example
• a post mitotic cell (ie a brain or muscle cell) does not divide- if its injured its lost
• premitotic cells (ie epithelial cells) can keep dividing

• are in every organ
• retain the ability to devide and differntiate and produce organs

if the cell is going to divide, it must reach a certain critical size before it can do so

• aka cell aging
• involves the hayflick number

• all cells that have the ability to divide will, but will slow down as they get older
• with each division a tiny part of the ends of chromatids are cut off, if the telomeres are at the end, the divisions will slow down
• the hayflick number is the number of times a cell can divide before slowing down
• changes based on the cell but is usually around 50

makes sure there is a balance between cell multiplaction and cell death

cell induced death due to a programmed mechanism which activates suicide enzymes

ie estrogen regulates endometrial growth

when normal cells grow, once they touch eachother they will stop growing

• the specializing of a cell as far as function is concerned
• results from inactivation of particular genes
• produces populations of cells with limited capabilities
• differentiated cells form tissues

• in the zygote, you have cell lineages and each lineage starts specializing to form certain organs with specialized functions
• you take the same genetic makeup but inactivate certain genes in some places and other genes in other places to get specialized function
• ie all the diff wbcs function differently bc they have different genes turned off

• molecular level
• organelle level
• cell level
• tissue level
• organ level
• system level
• organism level

• epithelial
• connective
• muscle
• nervous

• 23 sets of chromosomes
• things are normal

• not having euploidy
• having extra or missing chromosome (s)

• relaxed normal respiration (12-15/min)
• really 12-20

• breathing cessation
• due to hypocapnia (reduced co2 in blood)

• shortness of breath
• in pregnancy, obesity, affected by posture

• difficulty breathing
• labored breathing
• air hunger
• in COPD common

• 6 breaths per min
• do to hypocapnia

• severe hypoxia
• in COPD

• hypoxia: low o2 at tissue level
• hypoxemia: low o2 in arterial blood

• breathing more than 25/min
• due to hypercapnia

a 5mmHg increase in PCO2

air in the interpleural space

• lung collapse
• blebs, gunshot: a tear in visceral pleura

• restrictive airway diseases
• obstructive lung diseases
• infections

• reduced expansion of the lung which means reduced total lung capacity
• conditions where the alveolar space is occupied or the area of the alveolar space membrane is restricted and not available for gas exchange
• trouble fully expading the lung

• edema
• ARDS
• pneumothorax
• Infant respiratory distress syndrome

you have a problem getting air in and out

• asthma
• childhood asthma
• COPD- chronic bronchitis
• COPD- emphysema
• Cystic fibrosis

• pneumonia
• tuberculosis

• excessive water in the lungs that cant be drained away as fast as the lymphatic system would try to do so
• overwhelms the lymphatic system and fluid accumulates

• increased hydrostatic pressure: causes fluid starts leadking out from volume overload
• decreased serum albumin: bc the blood cant hold fluid and it leaks out. The lower albumin makes water not come into the blood
• lymphatic obstruction: if lymph cant drain the lungs, fluid will accumulate and cause edema
• pulmonary hypertension: narrowing of pul blood vessels, hypertrophy of smooth muscles or fibrous lesions around muscles- fluid will leak in
• increased capillary permeability: due to injury of membranes by infections, virus or inhaled gases
• aspiration: gastric/drowning
• drugs: shock/trauma/sepsis/radiation
• undetermined: high altitude

the capacity for gas exchange is impacted and respiratory function is compromised

• neprhotic disease: albumin is lost in the uring
• liver disease: liver cant produce albumin
• low albumin [] means water leaves blood and enters lungs

• heart disease
• ARDS/Toxic gases
• Lymph blockage

all of these cases end up with altered pulmonary function bc of edema in lungs

• Acute Respiratory Distress syndrome
• generally associated with infection, trauma, inhalation of fluid or toxic smoke/gas, drug overdose or interactions, or multiple blood transfusions
• you need to suspect it quickly bc theres a high death rate

• there is usually an injury of septal membrane of alveoli and the blood vessels and bc of the injury to the septal membrane of the alveoli and to the blood vessels so you get increased permeability across alveolar/vascular membrane so you end up with leakage and fluid getting into the alveoli, which initiates an inflammatory reaction
• bc of the inflammatory rxn you start the calling of inflammatory cells 
• fibrosis (formation of excess fibrous connective tissues in an organ or tissue when trying to repair or reactivate a process)- you may end up with permanent lung dmage
• fluid in the lungs (similar to that in congestive heart failure), you can hear crackles and wet breath sounds (rales)

The difference of pulmonary artery pressure- elevated in heart failure with a weakened left ventricle where here its not elevated

• will happen 24-48 hours after er admission
• bilateral fluffy infiltrates on xray - may progress to a whiteout and under these conditions it becomes indistinguishable from CHF
• pao2: 52 - hypoxic
• PAO2/FIO2 ratio: less than 200 (these values are the basis of diagnosis)

• acute lung injury, which may progress to ARDS
• usually under these conditions and ards, pulmonary artery wedge pressure is normal, it wouldnt be in CHF

• Diffuse injury to the lungs
• infection, sepsis, pancreatitis, surgery
• head or chest trauma
• toxic smoke/fluid drowning, aspiation
• drugs
• multiple blood transfusion

• you get injury to the lungs by various causes and bc of that you get damage to endothelial cells and to the alveolar epithelial cells
• the damage to the endothelium will result in a massive inflammatory resonse, calling of PMNs, release of cytokines and eventual leakage causing pulmonary edema in the alveolar space, this will lead to ventilation impairment and cause ARDS
• also endothelial damage causes vasoconstriction which decreases perfusion and leads to ards
• The damage to the alveolar epithelial cells will have damage to the alveoli and the type II cells, so you are making the surface prone to bacterial infection s and also surfactant loss and adolectesis
• pneumonia and adolectasis together will lead to ARDS

so as you can see damage to 2 main parts causes ARDS in different ways (endo inflammation and epi pneumonia/adolectasis)

• SOB
• pale
• agitated
• lethargic or comatose
• cyanosis of extremities

these are all generally due to diffuse injury to lung tissue

• provide proper oxygenation by mechanical ventilation
• abx for sepsis or other infections
• cardiovascular support so vital signs are maintained

• Infant respiratory distress syndrom
• aka surfactant deficiency disorder
• an ARDS related disorder
• L/S ratio is less than 1.5 and PG is absent

• phospholipids
• pg is a phospholipid glcerol
• these are the ingrediants of surfactant

• Premature lungs= not enough surfactant= increase in alveolar surface tension, which leads to the alveolar membranes sticking to one another and the lungs stay stiff which causes the lungs to not be able to expand, which leads to adelectasis, which leads to uneven perfusion and therefore hypoventilation and hypopoxemia and co2 retnetion
• this retention causes acidosis which will affect surfactant synthesis further and cause pulmonary vasoconstruction leading to further pulmonary hypoperfusion which causes endothelial and epithelial damage and also more co2 retention which causes the plasma to leak into the alveoli and bc of that you will see fibrin and necrotic cells (aka hyland membrane formation) and that will compromise lung function further

• corticosteroids
• so its possible to induce their synthesis by providing corticosteroid injections to the mother at the appropriate time
• or you can give surfactant spray to the baby to expand lungs

• air in the pleural space
• types: primary spontaneous pneumothorax, secondary spontaneous pneumothorax, traumatic pneumothorax, tension pneumothorax, absorption pneumothorax

• in all of these types, air enters the pleural space and we get collapse of all or part of the lungs
• this can lead to painful breathing.