MEH session 6 Flashcards
Where is the spleen located?
Left upper quadrant of the abdomen
What is red pulp?
Sinuses lined by endothelial macrophages and cords
Red cells preferentially pass through here
Role:
Removed old red cells
Metabolises haemoglobin
What is white pulp?
Similar structure to lymphoid follicles
White cells and plasma preferentially pass through here
Role:
Synthesises antibodies
Removes antibody coated bacteria and blood cells
How does blood enter the spleen?
Splenic artery
How does blood leave the spleen?
Portal vein
What is the role of the spleen?
- old/abnormal red cells and platelets are removed by RES macrophages
- platelets and red blood cells can be rapidly mobilised during bleeding
- puriplotential stem cells proliferate during haematological stress or if marrow fails (myelofibrosis)
- Immunological - 25% of T cells here, 15% of B cells here. Important defence against encapsulated bacteria.
What is splenomegaly?
Enlargement of the spleen
Why might someone with splenomegaly experience a loss of appetite and weight loss?
The enlarged spleen impinges upon the stomach. The stomach cannot expand when food enters so they cannot eat as much.
Can the spleen be palpated under normal conditions?
No, it is never normal to palpate the spleen below the costal margin.
Where do you start to palpate the spleen?
Right iliac fossa
Where is the splenic notch?
Medial side of the spleen
How is an enlarged spleen measured?
Measure in cm from costal margin in mid-clavicular line
What causes splenomegaly?
- overworking red pulp eg. Haemolytic anaemia
- overworking white pulp eg. Infection with encapsulated bacteria
- back pressure - portal hypertension in liver disease
- extramedullary haemopoiesis - during haemotological stress/when marrow fails
- expansion due to infiltration of cells that shouldn’t be there
Eg. Leukaemia and lymphomas - expansion due to accumulation of waste products of metabolism
Eg. Gauchers disease, sarcoidosis
What is Gaucher’s disease?
A defect in the beta glucosidase enzyme which catakayses the breakdown of glucocerebroside (a constituent of red and white cell membranes) so cases glucocerebroside to accumulate in fibrils)
What are the consequences of splenomegaly?
Hypersplenism
Pancytopenia or thrombocytopenia can occur due to pooling of blood in the enlarged spleen
Risk of rupture if enlarged and no longer protected by rib cage. It is very vascular so this can cause excessive bleeding which may be fatal.
What can a ruptured spleen lead to?
- Haematoma formation which may lead to:
Anaemia
Hypertension in splenic artery - Infarction of spleen
Splenic artery is an end artery
What is hyposplenism and what does hyposplenism increase the risk of?
Reduced splenic function
Increased risk of overwhelming sepsis
What are the causes of hyposplenism?
Sickle cell disease - multiple infarcts and then fibrosis
Splenectomy - to prevent spleen from rupturing/tumour present
-coeliac disease
How does hyposplenism present on a blood film?
Howell-Jolly bodies - basophilic nuclear remnants (clusters of DNA) in circulating erythrocytes.
Normally during erythropoiesis, erythroblasts expel their nuclei but in some cases a small portion of DNA remains. Normally such cells would be removed by the spleen.
Which organisms are patients with hyposplenism particularly at risk of developing an overwhelming sepsis from?
Encapsulated organisms
- pneumococcus
- haemophilus influenzae
- meningococcus
What does cytopenia mean?
Reduction in number of blood cells
What does the suffix cytosis or philia describe?
An increase in the number of blood cells
Which leucocytes can be described as being a
Myeloid granulocyte
Basophils
Neutrophils
Eosinophils
Which leucocyte can be described as being an agranulocyte and myeloid?
Monocyte
Which leucocyte can be described as been an agranulocyte and lymphoid?
Lymphocytes
A neutrophil usually has 2-5 lobes in their nucleus. What are multiple lobules a sign of?
Vitamin B12 deficiency
Which is the most abundant leucocyte?
Neutrophils
How long do neutrophils usually live for?
1-4 days
How is neutrophil function controlled?
The glycoprotein, Granulocyte colony stimulating factor (G-CSF) which:
• Increases their production in bone marrow
• Decreases their maturation time
• Enhances chemotaxis and phagocytosis
When would you administer recombinant GCSF to a patient?
When they require more neutrophils
Severe neutropenia and sepsis
What are the common haematological causes of neutrophilia?
Myeloproliferative diseases - disease in which bone marrow makes too many blood cells
G-CSF in excess
What health behaviour can cause neutrophilia?
Smoking
What response mechanisms can cause neutrophilia?
(Bacterial) infection
Acute inflammation
Acute haemorrhage
Give an example of a drug that can cause neutrophilia?
Prednisone
What are the causes of neutropenia due to increased removal?
- immune destruction
- septic infection so neutrophils used
- splenic pooling
What are the causes of neutropenia due to reduced production?
- B12/folate deficiency
- infiltration by malignancy or fibrosis
- aplastic anaemia (empty bone marrow)
- drugs eg. Chemotherapy, antibiotics, anti-epileptics…
- viral infection - very common to have neutropenia following a viral infection (this is normal and not a bad thing)
- congenital disorders eg. Cyclic neutropenia
What are the consequences of neutropenia?
Life threatening bacterial or fungal infection
Mucosal ulceration - painful mouth ulcers
Which is the largest type of leucocyte?
Monocytes
Where is approximately half of the monocyte population stored?
Red pulp of spleen
What are the causes of monocytosis?
Chronic inflammatory conditions:
- rheumatoid arthritis
- lupus (SLE)
- crohn’s disease
- ulcerative colitis
Chronic infections:
- TB
- myeloproliferative disorders
- malignancies eg. Hodgkins disease, certain leukaemias
When do eosinophils play an important role?
• Important role in the immune response to multicellular parasites ◦ Helminths ◦ Roundworm ◦ Flukes • Important role in skin diseases: ◦ Bulbous pemphigold • Inappropriately activated in allergic diseases ◦ asthma ◦ Eczema ◦ Hayfever ◦ Urticaria ◦ Aspergillosis Hodgkins lymphoma
Therefore, usually these conditions cause eosinophilia
How do eosinophils work?
• Release of their granular contents which contains:
◦ enzymes such as elastase
◦ Reactive oxygen species
◦ Various leukotrienes and cytokines
Describe the function of basophils.
- Granules contain the vasodilator histamine and anticoagulant heparin
- These are released following binding of IgE to surface receptors
- Play an important role in parasitic and allergic reactions
What are the causes of lymphocytosis?
Viral infections Bacterial infections especially whooping cough Stress related- MI/cardiac arrest Post splenectomy Smoking Lymphoproliferative malignancies
Why would splenectomy cause lymphocytosis?
Lymphocytes not stored in spleen
What are the symptoms of pancytopenia?
• Anaemia ◦ Fatigue ◦ Dizziness ◦ Chest pain ◦ Shortness of breath • Thrombocytopenia ◦ Bleeding ◦ Bruising • Neutropenia ◦ Infection ◦ Ulcers fever
What are the causes of pancytopenia due to reduced production of blood cells in bone marrow?
B12/folate deficiency Malignancy or fibrosis Idiopathic immune aplastic anaemia Drugs Viruses Congenital bone marrow failure
Describe the composition of healthy bone marrow.
50% fat
50% haemopoietic cells
What is aplastic anaemia?
Pancytopenia with a hypocellular bone marrow in the absence of an abnormal infiltrate and with no increase in reticulin (fibrosis)
What are the different sources of haemopoietic stem cells?
- aspiration of bone marrow
- GCSF mobilised stem cells in the peripheral blood (collected by leucopheresis) eg. If donating stem cells to a sibling for a transplant or voluntary donor
- umbilical cord
What is used to match people for haemopoietic stem cells?
HLA type
28 year old woman presents to her GP complaining of marked tiredness. What should be done?
Nothing on note on clinical examination. No medication.
Full blood count
What is the mean corpuscular volume?
A measure of the average volume of a red blood cell. It is attained by dividing the haematocrit by the concentration of red blood cells.
The units of mean corpuscular volume are usually stated in fL (femtolitres). How many femtolitres are in a litre?
10 to the power of 15
What is the most common cause of portal hypertension?
Cirrhosis
What receptors detect painful stimuli?
Nociceptors
What are the two important control centres in the brain?
- hypothalamus in the diencephalon
- medulla oblongata in the brain stem
Is the set point of a control system always the same?
No, it varies over time
Give some examples of biological rhythms.
Circadian rhythm- Variations in cortisol throughout the day
Menstrual cycle - core body temperature varies during this cycle
How are biological rhythms controlled?
There is a biological clock in the brain composed of a small group of neurones in the suprachiasmatic nucleus in the hypothalamus.
Which hormone is important in setting the biological clock?
Melatonin released from the pineal gland
Why do people get jet lag?
Cues from the environment keep the biological clock on a 24 hour cycle. In a long flight, moving across a time zone results in a mismatch between environmental keys and the biological clock is disrupted.
When taking a sample of blood for cortisol measurement, why should the time of day be considered?
Cortisol concentrations vary throughout the day
Peak at 7am
Trough at 7pm
Give 2 examples of positive feedback in humans.
- Blood clotting - failure of this can cause haemorrhaging
* Ovulation - build up of FSH causes release of an oocyte from a follicle in the ovary
Give an example of negative feedback in humans.
• Response to hyperglycaemia
High concentration of sugar in blood
stimulates the release of insulin from beta cells in the islets of Langerhans in the pancreas
Insulin decreases the level of glucose in the blood
This returns blood glucose back o the
What is normal serum osmolality?
275-295 mOsmol/kg
How many g NaCL (molecular mass = 58.44 g/mol) would you add to 1 litre of deionised water to make a solution of 300 mOsmol/litre?
8.77g
What is the control centre in the regulation of blood osmolality and sodium ion concentration of blood plasma?
Osmoreceptors in the supraoptic and paraventricular nuclei of the hypothalamus
What are the effectors in the regulation of blood osmolality and sodium ion concentration of plasma?
Cells in the supraoptic and paraventricular nuclei of the hypothalamus detect a decrease in osmolality and sodium ion concentration of plasma which causes:
• Increased feeling of thirst
• Release of ADH (vasopressin) from the posterior pituitary gland
◦ This hormone acts on the kidneys
◦ Causes an increase in the permeability of the cortical collecting ducts of the nephrons to water
◦ Increases the reabsorption of water from the urine into the blood
What are the effects of ADH?
Acts on the kidneys
Causes an increase in the permeability of the cortical collecting ducts of the nephrons to water
Increases the reabsorption of water from the urine into the blood
After eating a meal, which hormone is released and from where is this hormone released?
Insulin is released from the pancreas
What are the effects of insulin?
Stimulates glycogenesis in the liver (via GLUT2-not insulin regulated)
Stimulates glucose uptake into tissues (GLUT4- insulin regulated in muscle and adipose tissue)
Therefore, plasma glucose declines.
When fasting, what hormone is released and from where is this released?
Glucagon is released by the pancreas
What are the effects of glucagon?
Stimulates glycogenolysis in the liver
Glucose is released into the blood. Plasma glucose increases.
Which glucose transporter is regulated by insulin?
GLUT 4
Present in muscle and adipose tissue
At what concentration is plasma glucose usually maintained?
Approximately 5mM
Define the term hormone.
Hormones are chemical messengers produced in endocrine glands or tissues that travel in the bloodstream to cause an effect on other tissues.
Apart from endocrine glands, other organs and tissues can secrete hormones. Which hormones are secreted by the: 1. Heart 2. Liver 3. Stomach 4. Placenta 5. Adipose cells 6. Kidney
- ANP and BNP
- IGF1
- Gastrin, ghrelin
- Inhibin, placental lactogen
- Leptin
- Erythropoietin, renin, calcitriol
What are the mechanisms of communication via hormones?
Autocrine
Paracrine
Endocrine
Neurocrine
Both neurones and endocrine cells can be depolarised.
True or false?
True.
Insulin
Glucagon
Growth hormone
are examples of which class of hormone?
Peptide/polypeptide
Which hormones are derived from tyrosine?
Adrenaline/noradrenaline
Thyroid hormones
What hormones are derived from tryptophan?
Melatonin
Are adrenal medulla hormones lipid or water soluble?
Water soluble
Are thyroid hormones lipid or water soluble?
Lipid soluble
Give some examples of hormones that are glycoproteins.
Luteinising hormone (LH)
Follicle stimulating hormone (FSH)
Thyroid stimulating hormone (TSH)
These are all secreted by the anterior pituitary gland
Steroids are all derived from…
Cholesterol
Give some examples of steroid hormones.
Cortisol
Aldosterone
Testosterone
The different classes of hormones are: Peptide hormones Glycoprotein hormones Amino acid derivatives Steroid hormones
State which are hydrophobic or hydrophilic.
Peptide- hydrophilic
Glycoprotein- hydrophilic
Amino acid derivates- can be either
Steroid- hydrophobic
Usually, the effect that a hormone has on a target cell depends on its concentration in the bloodstream. How is this different for lipophilic hormones?
Lipophilic hormones (steroids and thyroid hormones) bind specifically or non-specifically to proteins in the blood. Therefore, it is the concentration of unbound or free hormone that is biologically active. There is dynamic equilibrium between bound and free forms of hormone in plasma.
Which protein binds to thyroid hormones to transport them in the blood?
Thyroxine-binding globulin (TBG)
What are the roles of carrier proteins in the blood?
- increase solubility of hormone in plasma
- increase half-life
- readily accessible reserve
What determines the hormone levels in blood?
- Rate of production - synthesis and secretion is most highly regulated
- Rate of delivery - higher blood flow to a particular organ will deliver more hormone
- Rate of degradation - hormones are metabolised and excreted from the body
How do water soluble hormones exert their effect on an effector cell?
- GPCRs
- tyrosine kinase receptor
How do lipid soluble hormones exert their effect on effector cells?
- cytoplasmic receptor
- nuclear receptor
How do tyrosine kinase receptors work?
- dimerisation (except insulin receptor which is already dimerised)
- autophosphorylation of specific tyrosines
- recruitment of adapter proteins and signalling complex
- activation of protein kinase
- phosphorylation of target proteins
- cellular response
Where is the appetite centre and what is it composed of?
In the hypothalamus
The arcuate nucleus in the hypothalamus plays a central role and constrains primary neurones.
Secondary neurones in other areas of the hypothalamus receive inputs from the arcuate primary neurones and coordinate a response via the vagus nerve.
What are the different types of primary neurone in the arcuate nucleus?
- –>excitatory - stimulate appetite via the release of two peptides
- neuropeptide Y (NPY)
- Agouti-related peptide (AgRP)
- –>inhibitory - suppresses appetite by releasing:
- pro-opiomelanocortin (POMC) which yields several neurotransmitters including
- beta-endorphin
- alpha-melanocyte stimulating hormone (alpha-MSH)
Why is appetite suppressed and why do people get tired after a large meal?
In response to the stomach being filled with food, there is release of POMC by primary neurones in the arcuate nucleus of the hypothalamus.
POMC forms:
• Beta-endorphin - produces feelings of euphoria and tiredness
• ACTH
• Alpha-MSH - suppresses appetite
What does the hormone ghrelin do and where is it released from?
Peptide hormone is released from stomach wall when empty
Stimulates excitatory primary neurones in arcuate nucleus and therefore stimulates appetite
What does the hormone PYY do and where is it released from?
Peptide hormone released by the wall of small intestine
Activates inhibitory neurones in the arcuate nucleus of the hypothalamus so suppresses appetite.
Inhibits excitatory neurones in the arcuate nucleus of the hypothalamus so suppresses appetite.
What is the effect of leptin and where is it released from?
Peptide hormone- released by adipocytes in fat stores (level of leptin in the blood correlates with the amount of adipose tissue in the body)
Release is affected by: level of adipose tissue in the body
How does it work?
Activates inhibitory neurones in the arcuate nucleus - decreases appetite
Inhibits stimulatory neurones in the arcuate nucleus - decreases appetite
Induces the expression of uncoupling proteins in the mitochondria leading to the production of heat rather than ATP
How is insulin involved in the control of appetite?
Peptide hormone - released by beta cells of the pancreas
Release is stimulated by: high blood glucose concentrations
Release is inhibited by: low blood glucose concentrations
How does it work?
Involved in short term and long term regulation of body weight and works in the same way as leptin but leptin has a more important role than insulin
Activates inhibitory neurones in the arcuate nucleus - decreases appetite
Inhibits stimulatory neurones in the arcuate nucleus - decreases appetite
What effect does amylin have on appetite?
Suppresses appetite
Which hormone communicates from the body to the hypothalamus to stimulate appetite?
Ghrelin
Which hormones communicate from the body to the hypothalamus to suppress appetite?
PYY
Leptin
Insulin
Amylin
Lack of production of which hormone has been associated with obesity?
Leptin acts as a feedback mechanism from the body’s fat stores to control the level of intake of food. A lack of leptin production or insensitivity to leptin has been associated with obesity.
Has been used clinically to treat obese patients lacking the hormone
Which term is used to describe the communication pathway between a receptor and a control centre in the brain?
Afferent pathway
Which type of feedback is most common in biological systems?
Negative feedback
In which nucleus of the hypothalamus are the neurones that constitute the biological clock located?
Suprachiasmatic nucleus
In which nucleus of the hypothalamus are the neurones that regulate appetite located?
Arcuate nucleus
Which endocrine gland secretes the hormone melatonin?
Pineal gland
A solution of normal saline has a concentration of 308mOsmol/L. Do the units refer to osmolality or osmolarity of the solution?
Osmolarity
A solution of normal saline has a concentration of 398mOsmol/L
What concentration of Na+ ions would be in this solution?
154mM (mmol/L)
What term is used to describe low blood sodium?
Hyponatraemia
What effect would an increased concentration of ADH have on the reabsorption of water from urine into blood in the collecting ducts of the kidney?
Increased reabsorption leading to a smaller volume of more concentrated urine.
In which region of the brain are the osmoreceptors located?
Hypothalamus
Which term would be used to describe the mode of signalling in which a hormone acted over a short distance via interstitial fluid to affect a response on an adjacent or nearby cell?
Paracrine
Which class of hormone does cortisol fall under?
Steroid hormone
Which class of hormone does adrenaline fall under?
Amine hormone
Where is ADH synthesised?
Hypothalamus
Where is ADH released from?
Posterior pitiuitary gland
Which hormone is released from the stomach when it is empty in order to stimulate appetite?
Ghrelin
Which hormone is released from adipocytes and suppresses appetite?
Leptin
Which neurotransmitter is released from primary neurones in the arcuate nucleus of the hypothalamus to stimulate appetite?
NPY and AgRP
Name the peptide precursor of the neurotransmitters alpha-MSH, beta-endorphin and ACTH.
POMC
Infectious mononucleosis can cause the liver and spleen to become enlarged. What is infectious mononucleosis?
Glandular fever
Usually caused by Epstein-Barr virus
In young adults, results in fever, sore throat, enlarged lymph nodes
Primarily spread through saliva
What test can be used for diagnosis of glandular fever?
Paul Bunnel test to test for antibodies in patients serum
