Foundations of Medicine Block 1 Week 1 Flashcards
How many cells are there in the body ?
37 trillion cells in the body
What is another name for the colon ?
Large Intestine
What are the main layer of the large intestine wall ( from inner to outer)?
Mucosa (Most inner layer)
Submucosa
Muscularis propria
Subserosa
Serosa (outer layer)
What is the Mucosa layer of the wall of the large intestine made up of ?
Mucosa:
Epithelium
Connective Tissue
Thin muscle layer
What cells line the wall of the large intestine ?
Simple columnar epithelium
The intestinal villi are covered by two types of cell. What are these two types of cell ?
- Goblet cells - These are simple columnar epithelium cells whose sole function is to secrete mucin, whcih dissolves in water to from mucus.
2.Intestinal Absorptive cells - called Enterocyte
These are simple columnar epithelium cells.
Absorb molecules from the lumen including proteins, fats, sugars, water, electrolytes, vitamins and bile salts.
What are the functions of a cell?
- Division
- Differentiation
- Migration
- Adhesion
- Secretion
- absorption
- degradation
- sensing
- signaling
- survival
- death
What is a nucleus ?
Contains genetic information
Controls gene expression
Directs cells activities
What is an endoplasmic reticulum ?
Two types:
Rough endoplasmic reticulum
Smooth endoplasmic reticulum
Function:
Ribosomes are found on the rough endoplasmic reticulum
System for protein synthesis
Smooth Endoplasmic Reticulum (SER) function:
Synthesize steroid hormones from cholesterol
Manufactures carbohydrates and lipids
What is the Golgi apparatus ?
Stores and transports proteins
Transporting, modifying and packaging proteins and lipids into vesicles for delivery to targeted destinations
Lysosome enzymes are made by proteins from the endoplasmic reticulum and enclosed within vesicles by the Golgi apparatus.
Golgi apparatus form secretory vesicles which that migrate to the plasma membrane.
What are ribosomes ?
Ribosomes consist of proteins and ribonucleic acid (RNA)
They are formed in the nucleus and migrate to the cytoplasm .
Ribosomes function is to make new proteins
Some ribosomes become attached to the outer membrane of the endoplasmic reticulum to form the RER.
What is the Cytoskeleton ?
Cytoplasm and cytoskeleton are two components of a cell.
Cytoplasm is a fluid composed of cytosol , organelles, CYTOSKELTON and inclusions.
Cytoskeleton is composed:
Microtubules - play an important role in moving organelles
Intermediate Filaments - role in mechanical stability of cells
Actin Filaments - These play an important role in cell movement., such as the contraction of skeletal muscle.
They also help to keep cell shape in non-motile cells
What are Mitochondria ?
Oxidize glucose and fats to provide energy for other activities such as motility, synthesis of proteins, growth and repair.
The energy is provided by ATP.
The process of called ATP synthesis is called Oxidative Phosphorylation.
This takes place on the inner membrane of the mitochondria in a process known as tricarboxylic acid cycle and electron transport chain.
What is the function of the endocytic network ?
Take up and digestion
What are endosomes?
A vesicle formed by the invagination and pinching off of the cell membrane during endocytosis.
Endocytic pathway ?
Size at which we can see mitochondria using a microscope ?
2 micrometres
Describe the two main types of light microscopy ?
Bright - field light microscopy:
Used to image fluids and tissues samples
Often rely on dense stains incompatible with living cells
Fluorescence light microscopy:
Use a much higher intensity light to illuminate the sample.
Greater sensitivity : specify achievable (e.g. antibodies)
giving more precise localization (molecular level).
What is electron microscopy and describe the two main types ?
Electron microscopy (EM) is a technique for obtaining high resolution images of biological and non-biological specimens
As the wavelength of an electron can be up to 100,000 times shorter than that of visible light photons, electron microscopes have a higher resolving power than light microscopes and can reveal the structure of smaller objects
SEM - 10,000,000 x magnification
Light Microscope - 2000 x Magnification
TEM;
Beam of electrons is transmitted through the specimen to form an image
Requires a very thin specimen
SEM: is a type of electron microscope that produces images of a sample by scanning the surface with a focused beam of electrons. The electrons interact with atoms in the sample, producing various signals that contain information about the surface topography and composition of the sample.
Where does transcription from DNA to RNA occur?
Nucleus
What is Electron tomography ? (ET)
Detailed 3D structures of sub-cellular macro-molecular objects
Electron tomography is an extension of traditional transmission electron microscopy and uses a transmission electron microscope to collect the data.
Serial TEM collected data:
thousand of images from a sample taken at different depths/ angles and computer analysis reconstituting a static 3D view.
Exocytosis occurs by three pathways what are they ?
Constitutive and regulated
Lysosomes
Why do we need exocytosis and endocytosis ?
Polar molecules cannot penetrate through the lipid barrier of the cell membrane.
Polar molecules (such as digestive enzymes) are packaged in membrane-bound vescicels that can fuse
Why do we need exocytosis and endocytosis ?
Polar molecules cannot penetrate through the lipid barrier of the cell membrane.
Polar molecules (such as digestive enzymes) are packaged in membrane-bound vesicles that can fuse with the plasma membrane to release their contents into the extracellular space- this is known as exocytosis
What are the three exocytosis pathways ?
1.Constitutive exocytosis
2. Regulated exocytosis
3. Lysosome mediated exocytosis
Basic process of exocytosis:
Vesicles containing molecules are transported from within the cell to the cell membrane.
The vesicle membrane attaches to the cell membrane.
Fusion of the vesicle membrane with the cell membrane releases the vesicle contents outside the cell.
Constitutive: involves regular secretion of molecules. This action is performed by all cells.
Regulated: relies on the presence of extracellular signals for the expulsion of materials within the vesicles.
Does not occur in all cells. Mainly only secretory cells.
Secretory cells store products such as hormones, neurotransmitters and digestive enzymes that are released when triggered by extracellular signals.
Lysosomes: Carry digested material to the cell membrane where they fuse with the membrane and release their content into the extracellular matrix.
What are the 4 pathways of endocytosis ?
1.receptor-mediated endocytosis (also known as clathrin-mediated endocytosis) - takes in most things. There are 20 receptors which works this way.
2. caveolae - take in nanoparticles.Particles usually 50-100 nanometres.
3. pinocytosis - take in fluid with dissolved small molecules.
4. phagocytosis - part of the immune system. Ingest particles larger than 50 micrometres into a phagosome.
What is endocytosis ?
Endocytosis is used by cells to retrieve components of the plasma membrane and to take up macromolecules from the extracellular space.
What is phagocytosis ?
Phagocytosis is a specialized form of endocytosis in which large particles (e.g. bacteria or cell debris) are ingested by phagocytes.
The pri
What are peroxisomes?
Peroxisomes are small membrane enclosed organelles that contain enzymes (at least 50 different enzymes) involved in a variety of metabolic reactions, including several aspects of energy metabolism.
Site of oxidative reactions with hydrogen peroxide production.
Hydrogen Peroxide is then converted into water and oxygen.
Another site of fatty acid metabolism.
What are the 3 ways cells communicate with each other ?
- By diffusible chemical signals - allows cells to communicate at a distance
- By direct contact between the plasma membrane of adjacent cells - important in cell-cell recognition during development.
- By direct cytoplasmic contact via gap junctions - permits the electrical coupling of cells and plays an important role in the spread of excitation between adjacent cardiac muscle cells.
In which 3 ways to cells use diffusible chemical signals ?
- Paracrine signaling - when the secreted signal acts on cells nearby (local). The signaling molecules are destroyed rapidly by extracellular enzymes or by uptake into the target cells. Consequently very little of the secreted material enters the blood.
- Endocrine signaling - Hormones are secreted into the blood by endocrine glands, to act on various tissues around the body. (not localized). Because hormones are circulated their actions are often slow and long-lasting ( ranging from seconds to hours)
- Synaptic Signaling - Nerve cells release chemicals at their endings to affect the cells they contact.
Give two examples of Paracrine signaling ?
- Prostaglandins secreted by a cell act on neighboring cells to stimulate them to produce more prostaglandins.
2.Mast cells in tissues have secretory granules which release histamine. Histamine dilates local arteriole and increases the permeability of local nearby capillaries.
Endocrine glands secrete hormones in response to a variety of signals. Give 3 examples of these?
- They may respond to chemical level in the blood. E.g. Insulin secretion from the B -cells of the pancreatic islets is regulated by the blood glucose concentration.
- They may respond to the level of other hormones in the blood. E.g. Sex hormones from the ovaries ( estrogen) and testes (testosterone) which are secreted in response to hormonal signals from the anterior pituitary gland.
- They may respond to the activity of nerves - this is how oxytocin secretion from the posterior pituitary gland and prolactin secretion by the anterior pituitary gland are controlled during lactation.
Which structure which releases hormones is an exception in the endocrine signaling pathway?
The releasing hormones of the hypothalamus. These hormones are released into portal blood vessels and travel to the anterior pituitary gland where they control the secretion of the anterior pituitary hormones.
Will any cell respond to a hormone ?
No the only cell types which respond to hormones are the cells which have the correct receptors.
Also the receptors must have a high affinity for that particular hormone.
How do we know if a chemical is acting as a endocrine or paracrine signal ?
If sufficient quantities of a signaling molecule are released that it is able to affect tissues remote from the point of secretion it is being employed as a hormone.
Whereas if the amounts secreted are sufficient only to affect the cells close to the point of secretion, the chemical signal is acting as a paracrine signal.
What is Acetylcholine’s
2) Physiological role and mode of action
2) Synaptic signaling molecule, opens ligand-gated ion channels and also activates G-Protein linked receptors
What is Adrenaline ( epinephrine)
2) physiological role and mode of function
2) Hormone , wide variety of effects, acts via G-protein linked receptors
What is Antidiuretic Hormone (ADH, vasopressin) :
2) physiological role and mode of fuction
2) Hormone, increase water reabsorption by collecting tubule of the kidney via G-protein linked receptor
What is Insulins:
1) Physiological role and mode of function
1) Hormone, activates catalytic receptors in the plasma membrane, increases uptake of glucose by the liver, fat and muscle cells.
What is Somatostatin:
1) Physiological role and mode of function
1) Hormone and local mediator, inhibits secretion of growth hormones by anterior pituitary gland via G-protein linked receptor.
Which type of signaling molecules can diffuse straight through the plasma membrane:
Water loving / polar - molecules can not easily diffuse across the cell membrane e.g. glucose and ions
Water hating/ non polar - molecules can easily diffuse across the cell membrane e.g. urea
Remember the inside of the cell membrane is water hating
What are drugs that activate a particular receptor called ?
Agonists
What are drugs that block a particular receptor called ?
Antagonist
What are drugs that block a particular receptor called ?
Antagonist
How do receptors control the activity of target cells ?
- Open an ion channel - Nicotinic ACh receptor
- It may directly activate a membrane bound enzyme - insulin receptor
- It may activate a G-protein - linked receptor that may modulate an ion channel or change the intracellular concentration of a specific chemical, called a second messenger. The original signaling molecule is the first messenger. - Muscarinic ACh receptor.
- The signal may act on an intracellular receptor to modulate the transcription of specific genes. - Eostrogen receptor
What are ligand - gated ion channels ?
Receptors which are directly coupled to ion channels.
Ligand gated ion channels are open for a short period of time following the binding of their specific agonist, this alters the membrane potential of the target cell.
What does activation of ligand - gated ion channels do to the target cell ?
Depolarizes the target cell. The depolarization activates voltage - gated ion channels which trigger the appropriate cellular response.
What are catalytic receptors ?
Catalytic receptors are membrane bound protein kinases that become activated when they bind to their specific ligand.
A typical example of a catalytic receptor is the insulin receptor that is found in the liver, muscle and fat cells.
The receptor is activated when it binds insulin and in turn activates other enzymes by adding a phosphate group to tyrosine residues.
This results in an increase in the activity of the affected enzymes which culminates in an increase in the rate of glucose uptake.
What are the 3 main classes of membrane lipids ?
- Phospholipids
- Glycolipids
- Cholestrol
What are the two types of phospholipid?
Which is more abundant in cell membranes ?
- Glycerophospholipid
- Sphingolipids
Glycerophospholipid are more abundant
What determines the fluidity of a cell membrane ?
The amount of lipids.
The more cis -double bonds in a fatty acid the more fluid the cell membrane and the lower its melting temperature
Most phospholipids have a saturated fatty acid chain in the C1 position and a cis-unsaturated fatty acid in the C2 position of the glycerol backbone.
What are the 3 major classes of membrane transport proteins ?
Transporters - bind only one substrate at a time, transport membrane across molecule passively - facilitated diffusion
ATP powered pumps - ATPases that use energy of ATP hydrolysis to move ions or small molecules across membrane against a chemical concentration gradient - active transport
Channel proteins - water filled pores, when opened ions move down their concentration gradient
What are uniporters ?
Move one molecule at a time down their concentration gradient
What are symporters ?
A symporter is an integral membrane protein that is involved in the transport of two different molecules across the cell membrane in the same direction
What are antiporters ?
Is the secondary active transport of two or more different molecules or ions across a phospholipid membrane such as the plasma membrane in opposite directions, one into the cell and one out of the cell.
How is glucose transported into a cell?
Using a uniporter carrier, down a concentration gradient.
GLUT4 transporter transports glucose into fat and muscle cells.
GLUT4 is transported to the membrane in response to insulin
Glucose is transported into the intestines using a different method. Glucose is actively transported into Intestinal cell using a cotransporter SGTL-1 (sodium glucose transporter) found in the apical membrane of enterocytes. This symporter uses the electrochemical gradient of two sodium ion to transport one glucose into the intestinal cell.
The second step is release of the intercellular glucose into the interstitial space, this is done by facilitated diffusion via the glucose transporter GLUT 2 in the basolateral membrane.
Give examples of steroids ? (can be steroid hormones)
- Cholesterol
- Bile salts
- Vitamin D
- Adrenocortical hormones
- Sex hormones
What does catabolism mean ?
The breakdown of molecules to obtain energy
What is anabolism ?
Anabolism is the set of metabolic pathways that construct molecules from smaller units. These reactions require energy, known also as an endergonic process. Anabolism is the building-up aspect of metabolism, whereas catabolism is the breaking-down aspect.
The synthesis of all compounds needed by cells
Describe glucose metabolism ?
Glycolysis is a set of reactions in which one glucose molecule is oxidised and two molecules of pyruvicacid are produced. The reactions also produce two molecules of ATP and NADH. IS Anaerobic Formation of acetyl CoA is a transition step that prepares pyruvic acid for entrance into theKrebs cycle. This step also produces NAD and oxygen.The Krebs cycle reactions oxidise acetyl CoA and produce CO2, ATP, NADH an FADH2 The ETC oxidisesNADH and FADH2 and transfer their electrons through a series of electron carriers.The Krebs cycle and ETC both require oxygen and as such are known as aerobic cell respiration
What enhances fat breakdown ?
Adrenaline and noradrenaline
Describe protein catabolism?
Proteins are broken down to individual amino acids using protease enzymes and HCL in the GIT.
Deamination (removal of amine group): These amino acids are broken down to a-keto acids ( by removing amine group) the left over which can be recycled in the body for energy and production of glucose or fat. This happens in the liver.
a-ketoglutarate enters the Krebs cycle to produce NADH and FADH2 which carry electrons to the electron transport chain to produce ATP via oxidative phosphorylation.
The amine group is now ammonia which is converted into urea.
Where does each step of glucose metabolism take place?
Glycolysis - cytoplasm
In glycolysis ATP is produced by substrate level phosphorylation phosphate groups are transferred to ADP. This occurs in the cytosol
Link reaction and Krebs cycle - mitochondrial matrix
ETC - mitochondrial cristae
What is ketogeneisis?
Ketogenesis is the biochemical process through which organisms produce ketone bodies by breaking down fatty acids and ketogenic amino acids. The process supplies energy to certain organs, particularly the brain, heart and skeletal muscle, under specific scenarios including fasting, caloric restriction, sleep, or others. (In rare metabolic diseases, insufficient gluconeogenesis can cause excessive ketogenesis and hypoglycemia, which may lead to the life-threatening condition known as non-diabetic ketoacidosis.They are acidic and as such can lead to acidosis if present in high quantities
Ketone bodies are produced mainly in the mitochondria of liver cells, and synthesis can occur in response to an unavailability of blood glucose, such as during fasting. There is a limit on how many can be oxidised with the main reason being the limit of oxaloacetate which isrequired to bond acetyl CoA before it can enter the citric acid cycle.Ketone bodies are converted to acetyl CoA and enter the Krebs cycle directly.30.Absorptive state
Examples of ketone bodies ?
Acetoacetic acid
Beta-hydroxybutyric acid
Acetone
What are the two main functions of metabolism ?
Anabolism
Catabolism
Metabolism is a balancing act involving two kinds of activities that go on at the same time: building up body tissues and energy stores (called anabolism) breaking down body tissues and energy stores to get more fuel for body functions (called catabolism)
How much grams of each macronutrient should a 17+ year old adult eat in a day ?
Carbohydrate - > 260g
Sugars 90g
Total fat <70g
Saturates <20
Protein 50g
Salt >6g
Dietary fiber 30g
What does the Uk diet actually look like?
- Over 10% calories come from free sugars
- Over 115 calories come from saturated fat
- Everyone in the UK eats well below the recommended amounts of oily fish
- Adult males exceed the recommendation for red and processed meat.
List some statistics to do with obesity in the UK?
- Only 26% of adults and 16% of children consumed the recommended amount of 5 portion of fruit and veg a day.
- 1 in 5 year 6 children are classified as obese
- 26 % of adults are classified as obese.
Describe lipolysis ?
Triglycerides are hydrolyzed into fatty acids and glycerol by lipase enzymes. This process is stimulated by glucagon and adrenaline.
The fatty acids bind to albumin so they become soluble in the blood and can be transported to tissues.
Fatty acids are oxidized by beta-oxidation in the mitochondria to generate ATP.
So fatty acids CANNOT be converted to glucose.
How much glycogen can be stored in the liver and muscle.
Liver: 100g
Muscle: 350g
Describe how different types of energy are used, how much and when ?
For a 65kg person
free glucose - 12g
Glycogen - 450g
Triacylglycerol - 15kg
Protein - 12.5kg
Glycogen is a short term energy store
Fat is a long term energy store
Protein acts a source of glucose in the absence of carbohydrate.
How much ATP is produced per molecule of glucose?
34 ATP
What are the products of the Krebs cycle?
3 NADH
FADH2
2 ATP
Describe anaerobic glycolosis ?
Anaerobic glycolysis serves as a means of energy production in cells that cannot produce adequate energy through oxidative phosphorylation. In poorly oxygenated tissue, glycolysis produces 2 ATP by shunting pyruvate away from mitochondria and through the lactate dehydrogenase reaction. In rapidly contracting skeletal muscle cells with energy demand exceeding what can be produced by oxidative phosphorylation alone, anaerobic glycolysis allows for the more rapid production of ATP.[3] (Glycolysis is approximately 100 times faster than oxidative phosphorylation.) In cells lacking mitochondria altogether, pyruvate cannot undergo oxidative phosphorylation regardless of oxygen levels.
Mature erythrocytes do not contain mitochondria and thus rely exclusively on anaerobic glycolysis for ATP production. Other tissues, such as the cornea and lens of the eye and inner medulla of the kidney, are poorly vascularized and rely heavily on anaerobic glycolysis despite the presence of mitochondria.
Glucose > (Glyceraldehyde dehydrogenase) > Pyruvate
. Instead of pyruvate being shunted to the mitochondria it is converted to lactate (by lactate dehydrogenase) with the generation of NAD+.
Glucose + 2ADP + 2Pi > 2 Lactate + 2 ATP + 2 H20
Lactate may be oxidized after conversion back to pyruvate, or converted back to glucose/glycogen in the liver (Cori cycle)
Describe the cori cycle?
Is a metabolic pathway in which lactate is transported to the liver and converted to glucose (gluconeogenesis).
Lactate gets to the liver via the blood.
Lactate > (lactate dehydrogenase) > Pyruvate
Pyruvate > ( glyceraldehyde dehydrogenase) > Glucose
This is a inefficient process for the production of useful energy in the cell.
The liver requires 6ATP to produce glucose from the liver whereas the return through glycolysis to lactate produces only 2 ATP.
Which tissues is glycolysis essential for?
Red blood cells (no mitochondria)
Kidney medulla ( blood supply poorer than cortex)
Eye lens (blood vessels & mitochondria would obscure light)
Hypoxic conditions at sites of injury or inflammation
Tumor cells use glycolysis to survive under hypoxic conditions ( a Hallmark of cancer)
Which substrates can be converted to glucose in the process of gluconeogenesis and which substrates cannot ?
Substrates which can:
Glycerol ( from triglycerides)
Amino acids ( from proteins)
Lactate
Fatty acids cannot be converted to glucose
Where are fatty acids oxidized and how ?
Fatty acids are oxidized by B oxidation in the mitochondria.
What is the pentose phosphate pathway ?
The pentose phosphate pathway is a metabolic pathway parallel to glycolysis.
There are two distinct phases in the pathway. The first is the oxidative phase, in which NADPH is generated, and the second is the non-oxidative synthesis of 5-carbon sugars. For most organisms, the pentose phosphate pathway takes place in the cytosol.
Pentoses: used for DNA/RNA synthesis
NADPH: used for lipid synthesis
What is the membrane potential ?
Active pumping of Na+ from a cell leads to a membrane potentialNa+ ions are actively pumped out of the cellThey become more concentrated in the extracellular fluid.The inner surface is more negatively charged and the outer surface is more positively charged. The difference in electrical charges between two regions constitutes an electrical gradient and because it occursacross the plasma membrane the charge difference is called the membrane potential.56.Coupled
What are the consequences of hypoglycemia ?
Stimulates the secretion of epinephrine, glucagon and HGH. As a consequence, anxiety, sweating, tremor,increased heart rate hunger and weakness occur.When blood glucose falls, brain cells are deprived of thesteady supply of glucose they need to function effectively. Severe hypoglycaemia leads to metal disorientation,convulsions, unconsciousness, and shock.
Pharmalogical effects of alcohol?
Acute
Slows done reflexes.
Induces sleep but not an ideal hypnotic.
Analgesic but not ideal.
Cardiovascular
Vasodilation
Tachycardia and mild rise in blood pressure.
Respiration
Stimulates respiration
BloodIncreases HDL cholesterol level
Decrease in LDL oxidation
Toxilogical effects of alcohol ?
Increased risk of heart disease
Dehydration
Central nervous system depression
Accumulation of acetaldehyde in the liver
Cirrhosis of the liver
Increased risk of cancer
Toxilogical effects of alcohol ?
Increased risk of heart disease
Dehydration
Central nervous system depression
Accumulation of acetaldehyde in the liver
Cirrhosis of the liver
Increased risk of cancer
How to work out units of alcohol?
Units = strength (ABV) x volume (ml) ÷ 1000
Pure alcohol is 100% ABV
