MEH session 6 Flashcards
1
Q
Where is the spleen located?
A
Left upper quadrant of the abdomen
2
Q
What is red pulp?
A
Sinuses lined by endothelial macrophages and cords
Red cells preferentially pass through here
Role:
Removed old red cells
Metabolises haemoglobin
3
Q
What is white pulp?
A
Similar structure to lymphoid follicles
White cells and plasma preferentially pass through here
Role:
Synthesises antibodies
Removes antibody coated bacteria and blood cells
4
Q
How does blood enter the spleen?
A
Splenic artery
5
Q
How does blood leave the spleen?
A
Portal vein
6
Q
What is the role of the spleen?
A
- 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.
7
Q
What is splenomegaly?
A
Enlargement of the spleen
8
Q
Why might someone with splenomegaly experience a loss of appetite and weight loss?
A
The enlarged spleen impinges upon the stomach. The stomach cannot expand when food enters so they cannot eat as much.
9
Q
Can the spleen be palpated under normal conditions?
A
No, it is never normal to palpate the spleen below the costal margin.
10
Q
Where do you start to palpate the spleen?
A
Right iliac fossa
11
Q
Where is the splenic notch?
A
Medial side of the spleen
12
Q
How is an enlarged spleen measured?
A
Measure in cm from costal margin in mid-clavicular line
13
Q
What causes splenomegaly?
A
- 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
14
Q
What is Gaucher’s disease?
A
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)
15
Q
What are the consequences of splenomegaly?
A
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.
16
Q
What can a ruptured spleen lead to?
A
- Haematoma formation which may lead to:
Anaemia
Hypertension in splenic artery - Infarction of spleen
Splenic artery is an end artery
17
Q
What is hyposplenism and what does hyposplenism increase the risk of?
A
Reduced splenic function
Increased risk of overwhelming sepsis
18
Q
What are the causes of hyposplenism?
A
Sickle cell disease - multiple infarcts and then fibrosis
Splenectomy - to prevent spleen from rupturing/tumour present
-coeliac disease
19
Q
How does hyposplenism present on a blood film?
A
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.
20
Q
Which organisms are patients with hyposplenism particularly at risk of developing an overwhelming sepsis from?
A
Encapsulated organisms
- pneumococcus
- haemophilus influenzae
- meningococcus
21
Q
What does cytopenia mean?
A
Reduction in number of blood cells
22
Q
What does the suffix cytosis or philia describe?
A
An increase in the number of blood cells
23
Q
Which leucocytes can be described as being a
Myeloid granulocyte
A
Basophils
Neutrophils
Eosinophils
24
Q
Which leucocyte can be described as being an agranulocyte and myeloid?
A
Monocyte
25
Which leucocyte can be described as been an agranulocyte and lymphoid?
Lymphocytes
26
A neutrophil usually has 2-5 lobes in their nucleus. What are multiple lobules a sign of?
Vitamin B12 deficiency
27
Which is the most abundant leucocyte?
Neutrophils
28
How long do neutrophils usually live for?
1-4 days
29
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
30
When would you administer recombinant GCSF to a patient?
When they require more neutrophils
| Severe neutropenia and sepsis
31
What are the common haematological causes of neutrophilia?
Myeloproliferative diseases - disease in which bone marrow makes too many blood cells
G-CSF in excess
32
What health behaviour can cause neutrophilia?
Smoking
33
What response mechanisms can cause neutrophilia?
(Bacterial) infection
Acute inflammation
Acute haemorrhage
34
Give an example of a drug that can cause neutrophilia?
Prednisone
35
What are the causes of neutropenia due to increased removal?
- immune destruction
- septic infection so neutrophils used
- splenic pooling
36
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
37
What are the consequences of neutropenia?
Life threatening bacterial or fungal infection
| Mucosal ulceration - painful mouth ulcers
38
Which is the largest type of leucocyte?
Monocytes
39
Where is approximately half of the monocyte population stored?
Red pulp of spleen
40
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
41
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
42
How do eosinophils work?
• Release of their granular contents which contains:
◦ enzymes such as elastase
◦ Reactive oxygen species
◦ Various leukotrienes and cytokines
43
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
44
What are the causes of lymphocytosis?
```
Viral infections
Bacterial infections especially whooping cough
Stress related- MI/cardiac arrest
Post splenectomy
Smoking
Lymphoproliferative malignancies
```
45
Why would splenectomy cause lymphocytosis?
Lymphocytes not stored in spleen
46
What are the symptoms of pancytopenia?
```
• Anaemia
◦ Fatigue
◦ Dizziness
◦ Chest pain
◦ Shortness of breath
• Thrombocytopenia
◦ Bleeding
◦ Bruising
• Neutropenia
◦ Infection
◦ Ulcers fever
```
47
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
```
48
Describe the composition of healthy bone marrow.
50% fat
| 50% haemopoietic cells
49
What is aplastic anaemia?
Pancytopenia with a hypocellular bone marrow in the absence of an abnormal infiltrate and with no increase in reticulin (fibrosis)
50
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
51
What is used to match people for haemopoietic stem cells?
HLA type
52
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
53
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.
54
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
55
What is the most common cause of portal hypertension?
Cirrhosis
56
What receptors detect painful stimuli?
Nociceptors
57
What are the two important control centres in the brain?
- hypothalamus in the diencephalon
| - medulla oblongata in the brain stem
58
Is the set point of a control system always the same?
No, it varies over time
59
Give some examples of biological rhythms.
Circadian rhythm- Variations in cortisol throughout the day
| Menstrual cycle - core body temperature varies during this cycle
60
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.
61
Which hormone is important in setting the biological clock?
Melatonin released from the pineal gland
62
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.
63
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
64
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
65
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
66
What is normal serum osmolality?
275-295 mOsmol/kg
67
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
68
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
69
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
70
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
71
After eating a meal, which hormone is released and from where is this hormone released?
Insulin is released from the pancreas
72
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.
73
When fasting, what hormone is released and from where is this released?
Glucagon is released by the pancreas
74
What are the effects of glucagon?
Stimulates glycogenolysis in the liver
Glucose is released into the blood. Plasma glucose increases.
75
Which glucose transporter is regulated by insulin?
GLUT 4
| Present in muscle and adipose tissue
76
At what concentration is plasma glucose usually maintained?
Approximately 5mM
77
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.
78
```
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
```
1. ANP and BNP
2. IGF1
3. Gastrin, ghrelin
4. Inhibin, placental lactogen
5. Leptin
6. Erythropoietin, renin, calcitriol
79
What are the mechanisms of communication via hormones?
Autocrine
Paracrine
Endocrine
Neurocrine
80
Both neurones and endocrine cells can be depolarised.
| True or false?
True.
81
Insulin
Glucagon
Growth hormone
are examples of which class of hormone?
Peptide/polypeptide
82
Which hormones are derived from tyrosine?
Adrenaline/noradrenaline
Thyroid hormones
83
What hormones are derived from tryptophan?
Melatonin
84
Are adrenal medulla hormones lipid or water soluble?
Water soluble
85
Are thyroid hormones lipid or water soluble?
Lipid soluble
86
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
87
Steroids are all derived from...
Cholesterol
88
Give some examples of steroid hormones.
Cortisol
Aldosterone
Testosterone
89
```
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
90
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.
```
91
Which protein binds to thyroid hormones to transport them in the blood?
Thyroxine-binding globulin (TBG)
92
What are the roles of carrier proteins in the blood?
- increase solubility of hormone in plasma
- increase half-life
- readily accessible reserve
93
What determines the hormone levels in blood?
1. Rate of production - synthesis and secretion is most highly regulated
2. Rate of delivery - higher blood flow to a particular organ will deliver more hormone
3. Rate of degradation - hormones are metabolised and excreted from the body
94
How do water soluble hormones exert their effect on an effector cell?
- GPCRs
| - tyrosine kinase receptor
95
How do lipid soluble hormones exert their effect on effector cells?
- cytoplasmic receptor
| - nuclear receptor
96
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
97
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.
98
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)
99
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
100
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
101
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.
102
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
103
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
104
What effect does amylin have on appetite?
Suppresses appetite
105
Which hormone communicates from the body to the hypothalamus to stimulate appetite?
Ghrelin
106
Which hormones communicate from the body to the hypothalamus to suppress appetite?
PYY
Leptin
Insulin
Amylin
107
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
108
Which term is used to describe the communication pathway between a receptor and a control centre in the brain?
Afferent pathway
109
Which type of feedback is most common in biological systems?
Negative feedback
110
In which nucleus of the hypothalamus are the neurones that constitute the biological clock located?
Suprachiasmatic nucleus
111
In which nucleus of the hypothalamus are the neurones that regulate appetite located?
Arcuate nucleus
112
Which endocrine gland secretes the hormone melatonin?
Pineal gland
113
A solution of normal saline has a concentration of 308mOsmol/L. Do the units refer to osmolality or osmolarity of the solution?
Osmolarity
114
A solution of normal saline has a concentration of 398mOsmol/L
What concentration of Na+ ions would be in this solution?
154mM (mmol/L)
115
What term is used to describe low blood sodium?
Hyponatraemia
116
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.
117
In which region of the brain are the osmoreceptors located?
Hypothalamus
118
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
119
Which class of hormone does cortisol fall under?
Steroid hormone
120
Which class of hormone does adrenaline fall under?
Amine hormone
121
Where is ADH synthesised?
Hypothalamus
122
Where is ADH released from?
Posterior pitiuitary gland
123
Which hormone is released from the stomach when it is empty in order to stimulate appetite?
Ghrelin
124
Which hormone is released from adipocytes and suppresses appetite?
Leptin
125
Which neurotransmitter is released from primary neurones in the arcuate nucleus of the hypothalamus to stimulate appetite?
NPY and AgRP
126
Name the peptide precursor of the neurotransmitters alpha-MSH, beta-endorphin and ACTH.
POMC
127
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
128
What test can be used for diagnosis of glandular fever?
Paul Bunnel test to test for antibodies in patients serum
