IMMS Flashcards
All lecture content other then Histology, critical numbers and public health
Name some supersecondary structures in proteins.
Helix-turn-helix, Beta alpha beta unit, leucine zipper, zinc finger.
What is a nucleotide?
A base joined to a sugar and any number of phosphates
What is a nucleoside?
A base with a sugar group
What are the base pairings (also RNA)?
A-T(U) G-C
What are the name of proteins that attach to DNA to make them coil?
Histones (bunch to make nucleosomes)
Which direction does DNA polymerase synthesise DNA
5’ to 3’
What is the function of Helicase
It unzips the DNA strands
What is the function of Topoisomerase?
It unwinds and relieves the supercoils of the DNA it is a Gyrase
What doe SSbs do?
They bind to the DNA to stop the strands annealing
Describe the process of transcription on the lagging strand
RNA primase lays primers for DNA polymerase in small sections cannot be done in one go like the leading. when the okazaki fragments are made DNA ligase joins the sections DNA polymerase replaces the RNA primers
What differentiates mature mRNA from full mRNA
the 5’ cap and the Poly A tail
What are the type of ribosomes in humans? and components
80S made from 60S and 40 S
what are the segments of tRNA?
Anticodon that binds to the strand.
Amino acid binding site opposite side.
D loop and T loop and a variable loop.
What are intorns and exons?
exons are exported to the final mRNA introns are discarded and broken down.
What are the characteristics of DNA?
Degenerate many AA are coded my more than one codon.
Unambiguous as each codon specifies only one AA
universal all organisms use the same.
Non overlapping each nucleotide is only read once.
What is a chromosomal abnormality?
An abnormality where there is the wrong number of chromosomes from non-disjunction or where large parts of the chromosome has been deleted
Name for trisomy 21
Down Syndrome
Which mode of inheritance allows direct male to male transmission?
Autosomal dominant
Features of autosomal recessive pedigree
“skipped generation”
males females affected equally
affected individual only in a single generation
Name some AR conditions
Cystic fibrosis, Sickle cell anaemia, Haemochromotosis, Tay-Sachs Disease, Connexin-26
Autosome
Any chromosome, other than the sex chromosomes (X or Y), that occurs in pairs in diploid cells
Recessive
Manifest only in homozygotes
Allele
One or more alternative forms of a gene at a given location (locus)
Homozygous
Presence of identical alleles at a given locus
Heterozygous
Presence of two different alleles at a given locus
Allelic heterogeneity
The situation where different mutations within the same gene result in the same clinical condition e.g. cystic fibrosis. Thus an individual with an autosomal recessive condition may be a compound heterozygote for two different mutations
Consanguinity
Reproductive union between two relatives.
Autozygosity
Homozygosity by descent, i.e. inheritance of the same altered allele through two branches of the same family.
If affected sibling how likely to be carrier in AR
2/3
Characteristics of AD pegigree
male to male transmission and female to female
affected individuals in multiple generations
male females equally affected
Penetrance
The percentage of individuals with a specific genotype showing the expected phenotype
Expressivity
Refers to the range of phenotypes expressed by a specific genotype
Recurrence risk
50% for transmission of mutation
BUT will the person be affected?
Depends on penetrance and expression
Anticipation
Whereby genetic disorder affects successive generations earlier or more severely, usually due to expansion of unstable triplet repeat sequences
Somatic Mosaicism
Genetic fault present in only some tissues in body.
Gonadal (germline) Mosaicism
Genetic fault present in gonadal tissue.
Sex-limited
Condition inherited in AD pattern that seems to affect one sex more than another
Late-onset
Condition not manifest at birth (congenital), classically adult-onset
Predictive testing
Testing for a condition in a pre-symptomatic individual to predict their chance of developing condition
Characteristics of X-linked inheritance pedigree
Only usually males affected
transmitted through unaffected females
no male to male transmission why?
Lyonization (X inactivation)
Generally only one of two X chromosomes active in each female cell. Can be skewed
List mendelian inheritance types
Autosomal dominant/ recessive
Sex linked
List non-mendelian inheritance types
Imprinting
Mitochondrial inheritance
Multifactorial
Genomic imprinting
to do with methylation of DNA etc
Homoplasmy
a eukaryotic cell whose copies of mitochondrial DNA are all identical (identically normal or have identical mutations)
Heteroplasmy
there are multiple copies of mtDNA in each cell
the name given to denote mutations which affect only a proportion of the molecules in a cell
the level of heteroplasmy can vary between cells in the same tissue or organ, from organ to organ within the same person, and between individuals in the same family
types of prenatal screening
Non-Invasive Prenatal Testing (NIPT) of blood looking for foetal DNA, amniocentesis, ultrasound
What are the roles of genetic testing?
To confirm a clinical diagnosis To give information about prognosis To inform management Allow pre-symptomatic/predictive testing in close relatives Carrier testing To give accurate recurrence risks Prenatal diagnosis
What is tested for in newboon heel prick?
Sickle cell disease, CF, congenital hypothyroidism, phenylketonuria (PKU) medium-chain acyl-CoA dehydrogenase deficiency (MCADD) maple syrup urine disease (MSUD) isovaleric acidaemia (IVA) glutaric aciduria type 1 (GA1) homocystinuria (pyridoxine unresponsive) (HCU)
What is analysis of chromosomes good for detecting
Chromosome number abnormalities, abnormalities in chromosome structure
what are FISH used for
Detection of abnormalites in number of chromosomes and microdeletions or duplications, can bee good for gene deletions.
What is a multi gene panel used to detect
single nucleotide changes
List benefits of Sanger sequencing/ disadvantages
Very accurate simple to read gold standard. but time consuming high cost per gene
What are the types of mutation
Deletion,inesertion, frame shift, splice site, missence, nonsence
What are incidental/secndary findings in a genetic test?
Additional findings concerning a patient or research participant that may, or may not, have potential health implications and clinical significance, that are discovered during the course of a clinical or research investigation, but are beyond the aims of the original test or investigation
What are targeted panels used for in genetic testing?
sequence a specific genes to look for specific mutations from a panel
what cell types can be genetically tested?
Blood (t lymphocytes) skin, umbilical cord, bone marrow, solid tumour, amniotic fluid,
how are chromosome abnormalities detected?
karyotype, comparing to ideograms, FISH, Microarrays
Describe what non-disjunction and how it can arrise in two forms
when there is an diffenet number of chromosomes in a cell. from meiosis one or two. in first anaphase or anaphase two both chromosomes/tids move to the same cell.
Trisomy 18
Edward’s syndrome
Trisomy 13
Patau syndrome
missing x/y
Tuners syndrome
what is triploidy
all chromosomes have three copies. results in miscarrage
What is obertsonian translation
when one of the chromosomes is added to another
what is Cri Du chat
5p deletion
Deletion 15q results in what condition?
Prada Willi/ Angleman syndrome
what is the resolution of microarys
5-10Mb mega bases
What is a constitutional genetic change?
Occurs at gametogenesis affects all of the body cells and is heritable
What is an aquired genetic change?
Occurs during lifetime, usually only affects some tissue and is non- heritable
what is a fusion/hybrid gene and how can it cause disease?
break points occur in the genes that creates a protein that behaves differently
what is a deregulation mutation?
Where a regulator gene is affected by a mutation and causes uncontrolled activity in the cell
What is an unbalanced genetic change?
One which changed the quantitiy of genetic material
What is a polymorphism?
A benign variant of a gene
What is splicing?
When exons are joined together
What is alternative splicing and where is it useful in the body?
Alternative slicing is the splicing of exons in a different order it can be useful in the prodction of antibodies
List many types of variant
Duplications of genes or part of gene
Deletions (whole gene or some exons)
Variants within the regulatory sequence
Splice site variants
Introduce premature stop codon-nonsense variant
Replace one amino acid in protein with another – mis-sense variant
Expansion of trinucleotide repeats
What is an out of frame deletion?
Out of frame deletion clearly disrupts the protein removes just one base and affects codons
What is an in frame deletion?
Where 3 bases or a multiple of 3 are deleted simply removing one codon.
Splice site variant
Affects the accurate removal of an intron
Non-sense variant
changes a codon to a stop one. this could be from out of fram deletion or single base change.
What is non-sense mediated decay?
when mRNA doesn’t have the correct ending which can be detected and this mRNA can be destroyed before it is translated
Mis-sence variants
single base substitution that changes the amino acid can be pathogenic of benign.
Name 3 diseases with expansion of tri-nucleotide repeat
Huntington’s disease CAG
Myotonic dystrophy CTG
Fragile X CGG
Anticipation
when a disease is onset earlier and more severely over time. Repeat gets bigger when transmitted to the next generation
and so symptoms develop earlier and are more severe
ALLELIC HETEROGENEITY
Lots of different variants in one gene e.g. cystic fibrosis
LOCUS HETEROGENEITY
Variants in different genes give the same clinical condition e.g. hypertrophic cardiomyopathy
Name the mechanisms of dominance
Loss-of-function variants
Only one allele functioning recessive.
If a pathway is very sensitive to the amount of gene product Haplo-insufficiency
Gain of Function variants
Increased gene dosage a variant may occur at the recognition site for protein degradation leading to an accumulation of undegraded protein within the cell
Dominant-negative variants
Where the protein from the variant allele interferes with the protein from the normal allele.
What is a diagnostic test?
Patient has signs and symptoms suggesting a particular diagnosis
A molecular genetic test will confirm a diagnosis
In this context a genetic test is being used to confirm a clinical diagnosis.
What is a predictive test?
Testing health at-risk family members for a previously identified familial variant – often dominant
HD No intervention
BRCA1/2 some intervention
What is carrier testing?
Autosomal recessive and X-linked disorder
Testing an individual in isolation not particularly helpful – couple testing
Reproductive decision making
What is Pre-natal testing
Genetic test performed in pregnancy where there is a increased risk of a specific condition affecting the fetus
Chorionic villous sample or amniocentesis
Often chromosomal or DNA if specific variant in the family has been identified
What is a multifatorial disease?
A disease whose severity is affected by genetic and envoronmental factors
How can genetic effect of a disease be studied?
twin studies
what are the characteristics of a multifactorial inheritance?
The incidence of the condition is greatest amongst relatives of the most severely affected patients
The risk is greatest for the first degree relatives and decreases rapidly in more distant relatives
If there is more than one affected close relative then the risks for other relatives are increased
What is a metabolic process?
In biochemistry metabolism is a sequence of chemical reactions: a particular molecule is converted into some other molecule or molecules in a defined fashion.
What are the 4 dietary metabolic pathways?
Biosynthetic
Fuel storage
Waste disposal
Oxidative processes
What is the cori cycle?
When 2 lactate is converted to 2 pyruvate then into 1 glucose by 6ATP where muscles are doing anaerobic respiration
Which of the following is a catabolic or anabolic process Storage ,Biosynthetic, Oxidative, Waste disposal?
Storage - anabolic
Biosynthetic - anabolic
Oxidative - catabolic
Waste disposal - (either)
Name 4 diatary fuels
Carbohydrates
Lipids
Proteins
alcohol
What is the energy per gram of Carbohydrate?
4kcal/g
What is the energy per gram of protein?
4kcal/g
What is the energy per gram of alcohol?
7kcal/g
What is the energy per gram of lipid?
9kcal/g
What is Basal metabolic rate?
A measure of the energy required to maintain non-exercise bodily functions such as; respiration, contraction of the heart muscle, biosynthetic processes, repairing & regenerating tissues, ion gradients across cell membranes.
What is the Average Basal metabolic rate with units?
1kcal/kg/hour
What condtions are needed for measuring BMR?
- Post-absorptive (12 hour fast)
- Lying still at physical and mental rest
- Thermo-neutral environment (27 – 29oC)
- No tea/coffee/nicotine/alcohol in previous 12 hours
- No heavy physical activity previous day
- Establish steady-state (~ 30 minutes)
- If any of the above conditions are not met, then = Resting Energy Expenditure (REE)
What factors affect BMR and how do they do this?
Increased age decreases BMR Gender Male is higher than female Dieting/ starvation decreases BMR Hypothyroidism lowers it Lower muscle mass causes lower BMR Increased BMI increases BRM Hyperthyroidism increases BMR Fever/ infection and disease increases BMR Caffeine/ stimulants and exercise also raise BMR
What happens to excess enerygy intake?
Store as triglycerides in adipose (approx 15kg),
Store as glycogen (up to 200g in liver & 150g in muscle), 80g in the liver after overnight fast,
Store as protein in muscle (approx 6kg).
Explain what happens during starvation in terms of hormones and energy sources.
lowered insulin increased cortisol. lipolysis and proteolysis consequently increase. Gluconeogenesis happens
after 4 days the liver produces ketones from fatty acids and brain starts to use ketones
Malnutrition
A state of nutrition with a
deficiency, excess or imbalance of
energy, protein or other nutrients,
causing measurable adverse effects
What are the dangers of re-feeding too quickly?
Re-feeding syndrome: Re-distribution of phosphate and magnesium due to insulin switch back to carbohydrates as the main fuel with requires more phosphate and thiamine.
What are essential fatty acids?
Ones that the body cannot synthesise itself. The main ones are polyunsaturated ones such as omega-3 and omega-6
What are some uses of trace elements and vitamins
Co-factors for metabolism (iron) gene espression, structural components, Antioxidants
What are the uses of Vitamin C (ascorbic acid)?
Heat labile
Collagen synthesis
Improve iron absorption
Antioxidant
What are the uses of Vitamin B12 cobalamin?
Protein synthesis, DNA synthesis, regenerate folate, nerve cells, fatty acid synthesis, energy production
What are the uses of Vitamin B1 thiamine?
helps with energy production
What are the uses of Vitamin D?
increases Ca absorption and helps deposit Ca and phosphate to teeth and bones.
how much protein should you take in?
0.8g/kg/day
What is the substrate of glycolysis?
Glucose
What mechanism is used in respiration for the “creation” of energy?
Substrate level phosphorylation
Describe the preparative step in glycolysis
Glucose is phosphorylated twice using ATP, by hexose kinase and phosphofructokinase-1
What is the ATP generating phase in glycolysis?
when glyceraldehyde 3 phosphate is oxidised by NAD+ and phosphorylated using inorganic phosphate
What is the name of the enzyme that converts glucose into glucose 6-phosphate?
hexokinase
What is glucokinase?
An enzyme in the liver that does same job as Hexokinase but has a much higher km
At what stage in glycolysis is the fate is the substrate committed to glycolysis?
When PFK-1 converts fructose 6-phosphate to fructose 1,6bisphosphate this process is irriversible and requries ATP
What happens once glucose is phosphorylated to glucose 6 phosphate?
Phosphoglucose isomerase converts it to fructose 6-phosphate.
How many molecules and at what stages are ATP required in glycolysis?
Hexokinase turning glucose into G6P. when PFK-1 converts fructose 6-phosphate into fructose 1,6-phosphate. these are the investment steps
What regulates PFK-1?
AMP increases its effects so does F1,6bisphosphate. ATP inhibits it as does citrate.
What is the rate limiting step of glycolysis?
PFK-1 converting fructose 6 -phosphate into fructose 1,6- phosphate.
what regulates hexokinase?
its product G6P
What is the name of the enzyme that converts fructose 1,6-phosphate into two triose phosphates?
Aldolase it is a reversible reaction.
What are the products of the aldolase enzyme?
glyceraldyhyde 3-phosphate and dihydroxyacetone phosphate
Which enzyme converts dihydroxyacetone phosphate to glyceraldehyde 3-phosphate
triose phosphate isomerase
Describe how Glyceraldehyde 3-phosphate is converted to 1,3-bisphosphoglycerate
inorganic phosphate and NAD+ are used with a glyeraldehyde 3- phosphate dehydrogenase to produce an NADH molecule and 1,3-bisphosphoglycerate
At which stages are high energy phosphate molecules made in Glycolysis?
in 1,3-bisohosohoglycerate as an acyl-phosphate and in phosphoenol-pyruvate as an enolic phosphate.
which stages in glycolysis produce ATP?
1,3-bisphosphoglycerate turning to 3-phosphoglycerate by phosphoglycerate kinase and phosphoenol-pyruvate turning into pyruvate by pyruvate kinase
what enzyme converts 3-phosphoglycerate to 2-phosphoglycerate?
phosphoglycerate mutase
what is the action of endolase?
It converts 2-phosphoglycerate into phosphoenol-pyruvate it produces water
What acts to regulate the action of pyruvate kinase?
ATP decreases its effect, fructose 1,6-bis phosphate also
What are the net products of glycolysis?
2ATP and 2NADH per molecule of glucose 2 pyruvate
What happens to NADH when aerobic respiration cannot take place?
It is used to reduce pyruvate to lactate which oxidises the NADH to NAD+ which can be used in glycolysis again.
Which tissues rely on anaerobic glycolysis and why?
Red and white blood cells, kidney medulla and sometimes muscles. in RBC there is no mitochondria so this is only source of ATP
Where in the cell does glycolysis take place?
In the cytosol/cytoplasm.
What is the action of Adenylate kinase?
2 ADP AMP+ATP to keep balance
Where does the citric acid cycle take place?
In the cytosol of the mitochondria aka the matrix
How does pyruvate enter the TCA cycle?
It is transported across the mitochondrial membranes inside it is converted to acetyl co-A a CO2 molecule is lost and a reduced NAD is formed. pyruvate dehydrogenase inhibited by products
What are the products of one turn of the TCA cycle?
2x CO2 3x NADH 1x FADH 1x GTP
Name the chemical intermediates in Krebs’ cycle in order
Oxaloacetate, Citrate, Isocitrate, Alpha-ketoglutarate, Succinyl-CoA, Succinate, Furmate, Malate
Which enzyme joins oxaloacetate with acetyl-CoA?
Citrate synthase
What does aconitase do?
Converts citrate into isocitrate.
What converts isocitrate into alpha-ketoglutarate and what are the products?
isocitrate dehydrogenase which produces CO2 and NADH
What converts alpha-ketoglutarate into succinyl-CoA?
alpha-ketoglutarate dehydrogenase and it produces CO2 and NADH
What does Succinyl CoA thiokinase do?
converts succinyl-CoA into succinate producing a GTP
What happens to Succinate in the TCA cycle?
it is dehydrogenated to furmate by succinate dehydrogenase producing an FADH2
What converts furmate to Malate?
furmase and water is added to it
How is oxaloacetate regenerated in the last step?
malate dehydrogenase converts malate to oxaloacetate while producing NADH
What inhibits citrate sythase?
high citrate concentration, NADH which also affects the amount of malate and oxaloacetate.
What are the rate limiting steps of the citric acid cycle?
Isocitrate dehydrogenase which is activated by ADP and inhibited by NADH, and by succinyl Co-A
Which enzyme is activated by Ca2+?
alpha-ketoglutarate dehydrogenase
What are the sources of fatty acids?
from triglycerides and phospholipid.
What is a carnitine shuttle?
It moves fatty acids that are more than 14 carbons long across the mitochondrial membrane.
Describe the structure and function of a chylomicron
It is made of fatty acids and cholesterol and apoproteins which carry lipids in the lymphatic system and the bloodstream.
Describe fatty activation
ATP is added to a fatty acid to turn it into acyl adenylate and an inorganic phosphate is released. then Coenzyme A is added to produce acyl-CoA
What is the purpose of fatty acid beta-oxidation?
To produce acetyl CoA that can be used in the krebs cycle
Outline the process of beta-oxidation
A long acyl-CoA is split into many smaller acetyl-CoA molecules
What are the stages of fatty acid oxidation?
First one of the carbons 2nd to the Co-A is dehydrogenated to make a double bond. then water is added to make an alcohol group. Then that is oxidised to a double bond O. Then the acetyl-CoA is released and an acyl-CoA
Which enzyme creats the double bond on the beta carbon in fatty acid oxidation?
Acyl-CoA dehydrogenase it produces an FADH2
What is the function of Enol-CoA hydrate?
it adds a water to the double bond to produce an alcohol.
What is the function of Hydroxyacyl CoA-deydrogenase?
It oxidises the OH to a O= and produces an NADH
what is the action of Thiolase?
It separates the Acetyl-CoA from the acyl and adds a CoA to the remaining acyl
Where does beta oxidation of fatty acids take place?
In the matrix of the mitochondria
What happens if there is an excess of acetyl CoA?
it can be converted into ketones
Name the three ketones we can synthesise
Acetone, acetoacetate and betahydroxybutyrate
What regulates ketogenesis?
overloading of TCA cycle
When there is a lot of free fatty acids increased ketogenesis, a low concentration of G3P in the liver increases ketones
when we need a lot of ATP ketones are not produced. Fatty acid oxidation is dependent on the amount of glucagon which activates it whereas insulin inhibits ketone production.
when demand for ATP is high
What is the clinical significance of Ketogenesis?
normally ketones are produced in low levels. if there is a shortage of carbohydrates then fatty acids are released. excess ketogenesis can cause ketoacidosis.
What are the conditions can lead to ketoacidosis?
Chronic alcohol abuse, insulin dependant diabetics when not enough insulin given and newly diagnosed type 1 diabetics
Why does low levels of insulin cause production of ketone bodies?
insulin usually inhibits lipolysis enzymes so with lower levels lots of lipid is released causing high levels of fatty acids and acetyl CoA so TCA overload and increased ketone bodies
How does high blood ethanol concentration lead to ketogenesis?
high alcohol levels cause impared gluconeogenesis so low glucose and decrease insulin secretion which increases lipolysis and then too many fatty acids overload the TCA cycle.
What are the blood stats for ketoacidosis.
Low blood pH, high pO2 low pCO2 and low HCO3.
Membrane permeability is regulated by what?
transport proteins and the size of molecules.
What can membrane channels select for?
Size of molecule, the charge the voltage over the membrane
What type of transport do membrane channels allow?
passive diffusion
List the types of carriers across membranes and their functions?
Uniport- single substance
symport- two substances in the same direction
Antiport- two substances in the opposite direction
are carriers active or passive??
the can be either
Name the types of forces that drive movement across membranes.
Electrical gradients, electrochemical gradients chemical and electrical combined,
What are the types of passive and active transport across a membrane.
Passive: simple diffusion, facilitated diffusion.
Active: Primary, Secondary
What is simple diffusion?
When small/lipid soluble molecules pass through the membrane by diffusion down a concentration gradient alone. eg gases
What is facilitated diffusions?
this is when diffusion down a gradient is assisted by a protein carrier but no energy is expended
What is an example of facilitated diffusion?
Glucose transport into the cells
What is primary active transport?
Directly uses a source of ATP eg sodium potassium pump
What is secondary active transport?
It is when a substance is transported against its concentration gradient while another ion or product moves with its concentration gradient. eg sodium glucose co transporter in the renal tubules.
Describe some mechanisms of cellular signalling
intracellular peptide or steroid hormones. peptides happen on the surface. they can change genes
What is endocytosis?
transport into a cell through invaginations of the cell membrane.
What is the action of proton pump inhibitors?
Act on H+/K+ ATPase in gastric parietal cells to reduce acid production
What is the role of cholesterol in the phospholipid bilayer?
it regulates fluidity of the membrane
What is the general structure of a phospholipid?
fatty acid chain tail that is non polar and hydrophobic and a head which is a phosphate group which has a charge and is hydrophillic
What substances can pass freely though a phospholibid bilayer?
Water (aquaporins), CO2, N2 O2 small uncharged molecules like urea and ethanol.
Which types of substances cannot pass through a membrane?
Ions charged polar molecules or large molecules
What types of proteins can be present in a membrane?
Receptors, ATP driven transporters, Transporters, Ion channels, Self:non self proteins
why are membrane proteins needed?
cell polarisation and compartmentalisation.
What is the total water in a 70kg male?
42L
Which has the most water and what quantity intra or extracellular fluid?
Intracellular what is inside the cells at 28L
What is the volume of water in the extracellular fluid and what proportion of the total fluid is that?
14L 1/3 of the total water
What is intravasuclar fluid?
Fluid that is in the blood 3L
What is intersititial fluid and how much of it is there?
11L it is the fluid that is in tissues between the cells
What determines the movement of water between compartments?
the osmotic gradients
What are the main ions in the ECF?
Sodium, chloride and bicarbonate
What is the predominant ion in the intracellular fluid?
potassium
Which molecules contribute to the osmolarity of the ECF?
sodium ions glucose urea chloride and bicarbonate
What is the equation for plasma osmolarity?
2[Na]+2[K]+urea+glucose
what are some of the ways we can lose water?
Sweat, water vapour in breath, urine, faeces
why is water not given intravenously?
it is hypo-osmolar/ hypotonic meaning cells would burst near to it in the blood
What is the normal osmolarity of plasma
275- 295 mmol/kg
What is extracellular fluid?
plasma and intersitital fluid
How does the body react to dehydration?
It senses increased osmolarity in the ECF.
Anti-diuretic hormone(vasopressin) is released from the posterior pituitary.
This increases renal water retention by increasing reabsorption of water.
also stimulates thirst centre in the hypothalamus.
What is the action of ADH/ vasopressin?
It increases the permeability of the collecting ducts of the kidneys buy causing aquaporins to be added meaning more water is reabsorbed.
What does ACE do?
converts angiotensin 1 to angiotensin 2
Which organ produces angiotensinogen?
The liver
Which organ produces ACE?
The surface cells of pulmonary and renal endothelium.
what is the function of renin?
To cleave angiotensinogen into angiotensin 1
Name some of the effects of angiotensin 2
increase sympathetic activity, increase tubular sodium and chloride re absorption and potassium excretion and water retention, the adrenal gland cortex produces aldosterone to increase water retentionm the arterioles constrict to increase blood pressure. in sever cases ADH is secreted
What is the different between ADH and aldosterone’s action?
Aldosterone increases the volume whilst maintaining osmolarity by reabsorbing ions. Whereas ADH increases the volume and decreases osmolarity since it doesn’t reabsorb minerals as well.
What are some common causes of dehydration?
reduced water intake, vomiting diarrhoea, sweating
What are the signs of dehydration?
Thirst, dry mouth, inelastic skin, sunken eyes, raised haemocrit, weight loss, confusion, hypotension
What is the body’s response to water excess?
ECF osmolarity decreases, there are no thirst hormones released, there is inhibition of ADH production so the amount of urine passed is increased.
what are the consequences of excessive water intake?
Hyponatremia and cerebral overhydration which can cause headache confusion and convulsions.
What is volume overload and some common causes?
when there is too much fluid in the interstitial space. this can be caused by heart failure, kidney failure or cirrhosis
What happens during volume overload?
The interstitial volume is increased while the intravascular volume is decreased which causes increased ADH and aldosterone prodction which can worsen the symptoms leading to oedema
What is oedema?
excess accumulation of fluid in interstitial space
What are some general cases of oedema?
Loss of plasma protein, Inflamation: increased capillary permeability or obstruction of venous blood or lymphatic return.
What is serious effusion?
excess water in a body cavity
What is the mechanism for inflammatory oedema?
the vessels become inflamed and the spacese between cells increase which causes albumin to be released into the interstitial fluid.
what is venous oedema?
blood pools in the calves and causes higher pressure and the hydrostatic pressure is increased.
What is lymphatic oedema?
where the water is not as readily absorbed into the lymphatics system leading to oedema.
What is hypoalbuminaemic oedema?
When there are lower levels of albumin in the blood so the oncotic pressure is reduced.
What is a pleural effusion?
fluid outside the lungs.
Describe what transudate is?
fluid that is pushed through the capillary die to high pressure in the capillary and has a low protein content.
Describe exudate
it is fluid that has leaked around the cells due to inflamation and has a high protein content.
What is the relevance of sodium concentration levels?
It tells you the concentration but not the total body content as this is affected by the water quantities.
what are some causes of hypernatraemia?
Water deficit: poor intake osmotic diuresis, diabeties insipidus
Sodium excess: mineralocorticoid(aldosterone)
salt poisoning
What are some causes of hyponatraemia?
Artefactual from excess water.
sodium loss: diuretics, Addison’s disease
Excess water: IV fluids(iatrogenic) SIADH
what is a severe effect of hypernatraemia and hyponatraemia?
cerebral intracelllular dehydration (tremors, irritability, confusion) and for hypo cerebral intracellular overydration (headache, confusion, convulsions)
after fertilisation but before implantation describe the structure of the embryo
there is a group of amniotic cells forming a cavity, one outside this lining the trophoblast called the yolk sac and then the outer layer of trophoblast cells.
What is the name for the type of structure of the embryo before implantation?
the bilaminar disk
what are the three layers of the trilaminar disk?
the ectoderm in blue, the mesoderm in red, and the endoderm in yellow
Describe the formation of mesoderm
cells from the base of the primitive streak break of and migrate to between the two layers of the bilaminar disk. this is by day 17.
List some of the tissues the Ectoderm develops into.
Epidermis of skin, hair, nails Mammary, sweat and sebaceous glands Central nervous system Peripheral nervous system Pituitary gland Enamel of the teeth Lens of the eye and parts of the inner ear Sensory epithelium of nose, ear and eye
List some of the tissues the mesoderm develops into.
All of the musculoskeletal system
Deep layers of the skin
Abdominal and chest walls and lining
The walls of the bowel (but not the lining of the bowel)
The urogenital system
List some of the tissues the Endoderm develops into.
Epithelial lining of the gastrointestinal tract, respiratory tract and urinary bladder.
Parenchyma of the thyroid gland, parathyroid gland, liver and pancreas.
Epithelial lining of the tympanic cavity and auditory tube.
Plays a part in the development of the notochord.
Describe the formation of the notocord.
the endoderm fuses with the ectoderm and folds to form a tube separating the mesoderm into two halves. this is the notocord. there are areas of mesoderm that differentiate to become paraxial mesoderm while the other parts are called the lateral mesoderm.
How is the neurual tube formed?
the layer of cells above the notocord in the ectoderm converge to form the neurual fold and crests. one part forms a tube the other the neural crest the forms components of the PNS
where are somites derived from?
the paraxial mesoderm after the nevelopment of the neural tube.
What do somites become?
the myotomes
what produces dermotomes?
the ectoderm overlying the somites.
what is unique about each somite?
it is supplied by a single spinal nerve
What does the intermediate mesoderm give rise to?
urogenital system—the kidneys, the gonads, and their respective duct systems.
what does the lateral mesoderm give rise to?
Lateral mesoderm – splits into two layers;
The outer layer covers the inside of the chest and abdominal walls; the somatic (parietal) layer mesoderm.
The other layer covers the organs in the thorax and abdomen; the splanchnic (visceral) layer mesoderm.
How is the embryo folded?
In lateral folding the outer layers of amneaon fold to bring in part of the yolk sac to form the primitive gut made of endoderm.
Caudal folding: cranial area contains the mouth which needs moving to the front. heart needs moving down and brain up the tail end rolls up.
What has happened after a week in the embryonic development?
Fertilization, formation of the morula and blastocyst
What has happened after 2 weeks in the embryonic development?
Implantation of the blastocyst and formation of bilaminar embryonic discand early placenta
What has happened after 3 week in the embryonic development?
Differentiation of cell layers to form the tri-laminar embryonic disc
What has happened after 4 weeks in the embryonic development?
Folding of the embryoand continuing development
Of the three germ layers
What has happened after 5-8 weeks in the embryonic development?
Development of all organs
Which diseases are caused by endocrine failure?
Diabetes, thyroid disorders, acromegaly.
What is homeostasis?
Maintenance of a constant internal environment
What kind of things does your body control?
Temperature, pH, Blood pressure, Oxygen concentration, glucose and energy production or demans
How do cells communicate with each other to allow homeostasis to happen?
Endocrine, nerves and immune system.
What are the three types of signals in the body?
Electrical, Ions and Hormones
What are the three mechanisms of hormone communication?
Autocrine, paracrine, endocrine
What is autocrine communication?
A cell produces a signal and the signal stimulates a receptor on the surface of the same cell
What is paracrine communication?
Cells talking to neighbouring cells that are close to them. produces a signal that acts on a receptor that is close by
What is an example of paracrine hormones?
Acetylcholine in nerve cells and muscles
What is endocrine communication?
When a cell releases a hormone into the blood and then goes to a distant site to reach a target cell
Name some key endocrine organs
Hypothalamus, pituitary, thyroid, parathyroid, thymus, adrenal, pacreas, ovaries, testes
Explain the link between hypothalams and an endocrine gland?
Hypothalamus produces 6 main hormones, to the anterior pituitary it releases 6 main hormones and these can stimulate endocrine glands or affect target tissue directly
What are the hormones that the hypothalamus releases?
gonadotrophin-releasing hormone, Growth hormone-releasing hormone, Somatostatin, Thyrotropin-releasing hormone, Corticotropin-releaseing hormone and dopamine
What are the chemicals that the anterior pituitary releases?
Foliccle stimulating hormone, lutenising hormone growth hormone thyroid stimulating hormone, prolactin and adrenocorticotrophic hormone
What does the posterior pituitary do?
The hypothalamus uses special nerve cells to transmit the transmitter to send signals to the posterior pituitary it produces oxytocin and anti-diuretic hormone
What is a positive feedback loop?
a cell stimulates a cell and that cell does an action that stimulates the first cell.
What is a negative feedback loop?
A cell produces a hormone to stimulate a cell then this effect inhibits te orignal signal
What is the pituitary-thyroid axis?
Anterior pituitary reases thryoid stimulating hormone, then the thyroid produces thyroxine that affects cells, this thyroxin inhibits release of TSH it also inhibits the hypothalamus which stimulates anterior pituitary with thoxine releasing hormone. TSH can also inhibit the hypothalamus
What is the definition of a homone?
A molecule that acts as a chemical messenger
What are the three types of hormone?
Amino- acid derivative, peptide and steroid
How do peptide hormones work?
They produce a quick response like adrenaline, thyroid stimulating hormone is as well. they are hydrophilic and can be glycoproteins. they are synthesised from tyrosine. they bind to external receptors on cells
How do steroid hormones work?
Eg testosterone. It is produced in the testes and diffuses into the blood bound to transport proteins. it can pass though cell membranes into cells and the receptors are in the cell and it affects the DNA expression
What is a primary hormone problem?
Problem with the endocrine gland itself
What is a secondary hopothyroidism?
The initial problem is wih the pituitary or hypothalamus
What is simple diffusion?
High concentration to low concentration travell across the membrane, urea free fatty acids blood gasses water and ketone bodies
What is facilitated diffusion?
Glucose is transported down concentration by GLUT4 enzyme.
What is primary active transport?
Where ATP is used to pump something against its gradient
Secondary active transport?
It is where the gradient from one molecule is exploited to transport another in the opposite direction.
What molecules might be present on the membrane surface?
Ion exchange proteins, nutrient transport, self noself molecules ion channels g protein coupled receptors
What is para-cellular absorption?
When molecules are absorbed alongside the cells not from the apical surface
What are gap junctions?
allow flow of ions or molecules between the cytoplasm of two cells
What are methods of signal transduction?
steroid receptors in the nucleus, receptor linked ion channels in the membrane, G protein coupled receptors, some steroids can bind to receptors on the membreane, neurotransmitter receptors, growth factor receptors.
What is a G protein couples receptor?
The receptor is on the outside to recieve the signal, then there are three g protiens alpha beta gamma, alpha gives the specificity there is an enzyme that makes a second messenger often anenylyl cyclase that produces cAMP. can be inhibitory or exitatory
