Spleen, WBCs, Cytopenia and Endocrine Control of Appetite Flashcards

1
Q

What are the 2 types of tissue in the spleen and where does the blood go when it enters?

A

Red pulp, consisting of sinuses lined by endothelial macrophages and cords.
White pulp, with a similar structure to lymphoid follicles.
Blood enters via the splenic artery with WBCs and plasma preferentially passing through the white pulp and RBCs through the red pulp.

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2
Q

In children, the spleen is haematopoietic, what are its functions in an adult? (4-5)

A

Sequestration and phagocytosis - old/abnormal RBCs removed by macrophages.
Blood pooling, so platelets and RBCs can be rapidly mobilised during bleeding.
Extramedullary haemopoiesis - pluripotent stem cells proliferate and differentiate during haematological stress/if BM fails (myelofibrosis).
Immunological function - holds 25% T cells and 15% B cells. It’s needed to remove encapsulated bacteria and malaria.

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3
Q

What are you doing when looking for splenomegaly?

A

You can’t normally palmate the spleen below the costal margin, but you must start at the right iliac fossa (RIF), then edge up and to the left. Feel for splenic notch and measure in cm from the costal margin in the mid clavicular line.

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4
Q

Why might the spleen grow?

A

Back pressure (portal hypertension - liver disease),
Overworking red pulp (haemolytic anaemia),
Or white pulp (infection),
Reverting to extramedullary haemopoiesis,
Expanding as infiltrated by inappropriate cells (cancer cells of blood origin/metastases),
Or infiltrated by other material (Gaucher’s disease, sarcoidosis).

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5
Q

Aside from size, how may splenomegaly appear different on a scan?

A

It may be haemogenous or have attenuation (spots seen on a CT).

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6
Q

Spleen enlargement may be massive, moderate or mild, name some conditions that can cause each.

A

Massive: chronic myeloid leukaemia, myelofibrosis, chronic malaria, Schistosomiasis.
Moderate: as above and lymphoproliferative or myeloproliferative disorders,liver cirrhosis with portal hypertension, infections like Glandular fever caused by EBV.
Mild: as above and infections e.g. Hepatitis, endocarditis or infiltrative disorders e.g. Sarcoidosis or some autoimmune.

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7
Q

What is hypersplenism?

A

Pancytopenia or thrombocytopenia occurring due to a pooling of blood in an enlarged spleen.
(Also risk of rupture since no longer protected by rib cage, so avoid dangerous activities).

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8
Q

List some complications of hypersplenism.

A

Rupture leading to haematoma, infarction (repetitive) - functionally asplenic/hyposplenic e.g. Sickle cell.

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9
Q

What is hyposplenism and what may cause it?

A

Lack of functioning spleen tissue caused by a splenectomy, Sickle cell (older children/adults - multiple infarcts –> fibrosis), Coeliac disease.

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10
Q

What can cause patients to have Howell Jolly bodies seen on their blood filmand what are they?

A

Howell Jolly bodies are DNA remnants which look on a blood film like small purple dots. They appear when a patient has hyposplenism.

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11
Q

What are patients with hyposplenism at risk of?

A

Patients are at risk of overwhelming sepsis, particularly from encapsulated organisms, e.g. Pneumococcus, Haemophilius influenzae and Meningococcus.
Also, cytopenia - a reduction in the number of blood cells: anaemia, leukopenia, neutropenia, thrombocytopenia.

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12
Q

What is the opposite of cytopenia?

A

Cytosis/philia - increase in the number of blood cells with various forms: erythrocytosis, leukocytosis, neutrophilia, lymphocytosis and thrombocytosis.

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13
Q

Neutrophils are ___ responder phagocytes, the commonest ____ and an essential part of the ________ immune system. There maturation is controlled by the ________ hormone, which _________ production and decreases the time to release mature cells from the ______ _________ - they enhance chemotaxis, phagocytosis and killing of ___________.

A
1st
WBC
Innate
G-CSF
Bone marrow
Pathogens
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14
Q

Describe the pathway that produces neutrophils (from a myeloblast).

A

Myeloblast –> promyelocyte –> myelocyte –> metamyelocyte –> band (non lobed) –> neutrophil.

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15
Q

In which situations may recombinant G-CSF be administered?

A

If there is severe neutropenia and sepsis after chemotherapy (readily prescribed and can be self-injected).

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16
Q

List some causes of neutrophilia (including one haematological cause).

A

Acute inflammation, tissue damage, cancer, drugs (e.g. Steroids), infection (bacterial), acute haemorrhage, cytokines (G-CSF), smoking, metabolic/endocrine disorders and (haematological) myeloproliferative disorders, where the bone marrow overproduces.

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17
Q

Neutropenia is < 1.5 x10(9)/L and is severe if < 0.5 x10(9)/L. What are the 4 different ways it can come about?

A

Reduced production of neutrophils, increased destruction/use, benign neutropenia (Afro-Caribbean) or cyclic neutropenia.

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18
Q

In what way might neutropenia be caused by increased removal/use?

A

Immune destruction, sepsis or splenic pooling.

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19
Q

What could be the underlying cause of neutropenia by decreased production?

A

B12/folate deficiency, infiltration of bone marrow (malignancy/fibrosis), aplastic anaemia (empty bone marrow), radiation, drugs, viral infection or congenital disorders.

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20
Q

What are the consequences of neutropenia?

A

Severe bacterial/fungal infection, mucosal ulceration e.g. Painful mouth ulcers.
Neutropenic sepsis is a medical emergency and IV antibiotics must be administered immediately.

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21
Q

Monocytes respond to _________ and antigenic stimuli. They migrate to _______ where they become macrophages and their lysosomes contain ________, _______ proteins, IL, __________ acid and CSF. They can perform phagocytosis and ____________.

A
Inflammation
Tissues
Lysozyme
Complement
Arachiodonic 
Pinocytosis
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22
Q

What are the causes of monocytosis?

A

Chronic inflammatory conditions, chronic infection (TB), carcinoma and (haematological) myeloproliferative disorders/leukaemias.

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23
Q

Eosinophils have a lifespan of __ to ___ days and spend 3 to 8 ___ in circulation. They deal with some __________, mediate __________ responses and migrate to __________ surfaces. Their granules contain _______, phospholipids and _______. Also, they phagocytose ___________-__________ complexes and mediate _____________ reactions (drugs/asthma/skin inflammation).

A
8 to 12
Hours
Parasites
Allergic
Epithelial
Arginine 
Enzymes
Antibody-antigen 
Hypersensitivity
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24
Q

What are some causes of eosinophilia?

A
Allergic disease (eczema, hay fever etc), drug hypersensitivity (penicillin), Chaurg Strauss, parasitic infection, skin diseases.
Haematological causes: Hodgkin lymphoma, acute lymphoblastic leukaemia, acute myeloid leukaemia, myeloproliferative conditions, eosinophilic leukaemias and idiopathic hypereosinophilic syndrome.
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25
Q

Which granulocyte am I describing?
The least common but the biggest, black berry looking, active in allergic and inflammatory conditions. Has dense granules containing histamine, heparin, hyaluronic acid and serotonin.

A

Basophils.

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26
Q

What may cause basophilia?

A

From reactive (immediate hypersensitivity reactions, Ulcerative colitis or Rheumatoid Arthritis - unusual) or myeloproliferative causes.

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27
Q

Lymphocytes originate in the bone marrow, what are the B and T cells involved in?

A

B cells are involved in humoral immunity, with antibody/immunoglobulin forming cells.
T cells are involved in cellular immunity, with CD4+ helper cells, CD8+ cells and natural killer cells - cell mediated cytotoxicity.

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28
Q

Lymphocytosis can be reactive or lymphoproliferative (malignant); list some causes.

A

Reactive: viral infection, bacterial infection (especially Whooping cough), stress related (MI-cardiac arrest), post-splenectomy or smoking.
Lymphoproliferative: chronic lymphocytic leukaemia (CLL - B cells), T or NK cell leukaemias are less common or lymphoma (cells spill out of infiltrated bone marrow).

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29
Q

Pancytopenia can be caused by increased removal, what may underlie this?

A

Immune destruction (rare), splenic pooling, haemophagocytosis in bone marrow (rare).

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30
Q

Pancytopenia can be caused by reduced production, what may underlie this?

A

B12/folate deficiency, bone marrow infiltration, marrow fibrosis, idiopathic immune aplastic anaemia, radiation, drugs, viruses, congenital bone marrow failure (Falconi’s anaemia - may have double digit) - lose 50:50 fat to cells in bone marrow.

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31
Q

What’s aplastic anaemia?

A

Pancytopenia with hypocellular bone marrow in absence of abnormal infiltrate and no fibrosis/reticulin increase).

32
Q

Does haematological or non-haematological malignancy cause pancytopenia?

A

Either!

33
Q

What are the symptoms of pancytopenia?

A

Those of anaemia (fatigue, dizziness, chest pain, shortness of breath etc), those of thrombocytopenia (bleeding, bruising etc) and those of the underlying cause.

34
Q

What is a HPSC?

A

A haematopoietic stem cell has the greatest power of self renewal in adult tissue. It differentiates into a variety of different cells depending on stimuli and may mobilise out of the bone marrow, into the circulating blood and undergo apoptosis.

35
Q

HPSC/bone marrow transplants are mainstream haematological activities, what is the source?

A

Aspirate from bone marrow or G-CSF mobilised stem cells in peripheral blood, which get collected or umbilical cord stem cells at the time of normal delivery.
Siblings have a 1/4 chance of being a full HLA match.

36
Q

Mechanisms of homeostasis exist at all levels (cells, tissues, organ, organism). What do they do and why?

A

Act to counteract changes in the internal environment; variables are regulated so internal conditions remain stable and relatively constant - not a steady state, but a dynamic equilibrium. Failure leads to disease.

37
Q

What are the different components involved in homeostatic control?

A
  1. Stimulus
  2. Receptor detects stimulus - communication via afferent pathways (endocrine and nervous) to
  3. Control centre, determining the set point, analysing the input and determining the response, which communicates via efferent pathways (hormones or action potential)with
  4. Effector, causing change (then gives -/+ fb).
38
Q

The set point in a homeostatic system may vary with the Circadian/diurnal rhythm. What sets it off and where is it controlled?

A

The ‘biological clock’ in the brain exists in a small group of neutrons called the suprachiasmatic nucleus.
Zeitgebers (cues from the environment), keep the body on a 24hr cycle.

39
Q

Give some examples of Zeitgebers.

A

Light, temperature, social interaction, exercise, eating/drinking

40
Q

Which hormone is involved in setting the body’s diurnal rhythm and where is it released from?

A

Melatonin from the pineal gland is involved in setting the clock.

41
Q

What is the difference between positive and negative feedback?

A

Negative feedback responds in a way to reverse the direction of change and is the most common form in physiological systems. In contrast, positive feedback responds to change the variable even more in the direction of change (rare) and is used when rapid change is desirable, such as blood clotting or ovulation.

42
Q

Body water homeostasis is an example of a control system, where is the water in the body of a 70kg man?

A

42L of water.
28L intracellular and 24L extracellular.
11L interstitial and 3L in blood plasma (2L RBCs gives 5L blood).

43
Q

What measures the osmotic pressure of the blood plasma?

A

The hypothalamus’ osmoreceptors.

44
Q

Explain the difference between osmolarity and osmolality.

A

Osmolarity is the number of osmoles per L of solution.
Osmolality is the number of osmoles per kg of solution.
1mol = 6.02x10(23) particles. 1M solution = 1 mol of a substance in 1L.
Osmole = the amount of a substance that dissociates in a solution to form 1mol of osmotically active particles.

45
Q

1mM solution of NaCl has an osmolarity of 2mOsmol/L, what medical situation is present if there’s a serum osmolality of 275-295mOsmol/kg?

A

Hyponatraemia.

46
Q

What is the response pathwaybof the bosybto high plasma osmolality?

A

Water needs to be conserved.
It’s detected by osmoreceptors (hypothalamus), which leads to thirst and drinking to reduce osmolality, as well as triggering the posterior pituitary to produce more ADH, so there’s increased resorption of H2O from the urine into the blood by the collecting ducts of the kidney, meaning a small volume of concentrated urine.

47
Q

What is the response to the blood osmolality if the patient is hypotonic?

A

Low blood osmolality is detected (osmoreceptors in the hypothalamus), so the posterior pituitary secretes less ADH, meaning decreased resorption and a large volume of dilute urine.

48
Q

What’s the process of plasma glucose homeostasis involved when a meal has been eaten?

A

Plasma glucose concentrations rise above 5mM, so the beta cells in the pancreas secrete insulin, which stimulates glycogenesis in the liver and glucose uptake into tissues (by GLUT4) and plasma glucose declines.

49
Q

What’s the process of plasma glucose homeostasis involved when somebody is fasting?

A

Alpha cells in the pancreas secrete release glucagon, which stimulates glycogenolysis in the liver, so glucose is released into the blood and the plasma glucose increases.

50
Q

What is the endocrine system and what are hormones?

A

The endocrine system is a collection of glands and other tissues located throughout the whole body.
Hormones are chemical signals made in the endocrine glands or tissues that travel in the bloodstream to cause an effect on other tissues.

51
Q

Give some examples of the ‘other tissues’ that secrete hormones.

A

Heart tissue (ANP and BNP), the liver (IGF1), the stomach (gastrin and gherlin), adipose tissue (leptin) and the kidney (erythropoietin and renin) etc.

52
Q

What are the methods of communication that employ hormones?

A

Autocrine - hormone signal works back on the cell of origin.
Paracrine - hormone signal carried a short distance to adjacent cells through interstitial fluid.
Endocrine - hormone signal released into the bloodstream and carried to distance target cells.
Neurocrine - hormone originates in a neurone and after transport down an axon is released into the bloodstream and carried to distant targets.

53
Q

What similarities exist in the features of the nervous and endocrine systems?

A

Neurones and endocrine cells can both secrete and be depolarised, some molecules act as hormones and neurotransmitters, the mechanisms of action require interaction with specific receptors on target cells - both work in parallel for homeostatic control.

54
Q

Which 4 different groups are hormones classified into?

A
  1. Peptide/polypeptide- the largest group, with a short chain of amino acids, all water soluble.
  2. Amino acid derivatives - synthesised from aromatic amino acids with adrenal medulla hormones water soluble and thyroid hormones lipids soluble.
  3. Glycoproteins - Large protein molecules, often made of subunits, with carbohydrate side chains, all water soluble.
  4. Steroids - steroidogenic tissues convert cholesterol to different hormones, all lipid soluble.
55
Q

Class the following hormones: thyroid hormones, progesterone, growth hormones, noradrenaline/adrenaline, insulin, glucagon, LH/FSH/TSH, cortisol, aldosterone, melatonin and testosterone.

A

(Poly)peptides: insulin, glucagon and growth hormone.
Amino acid derivatives: thyroid hormone, NA/A (tyrosine) and melatonin (tryptophan).
Glycoproteins: luteinising hormone, follicle stimulating hormone and thyroid stimulating hormone.
Steroids: progesterone, cortisol, aldosterone, testosterone.

56
Q

Describe hormone transport mechanisms.

A

Some travel in the blood in simple solution (peptides, adrenaline), but most are bound (usually to proteins), which are often specific e.g. Thyroid hormone and thyroxine-binding globulin/TBG. There’s a dynamic equilibrium between bound and free forms of a protein in the plasma with only the free molecules biologically active.

57
Q

In terms of hormone transport, what’s TBG?

A

Thyroid hormone and thyroxine-binding globulin/TBG travel bound to one another in the blood.

58
Q

What are the roles of carrier proteins that bind hormones?

A

Increase the solubility of the hormone in the plasma, increase its half life and acts as a readily accessible reserve.

59
Q

What factors determine the hormone levels in the blood?

A

The rate of production (the most highly regulated), the rate of delivery (a higher blood flow to an organ delivers more) and the rate of degradation (metabolised and excreted).

60
Q

Hormones circulate in the blood at __________ concentrations and exert effects by _________ to specific receptors, which ________ cells express, leading to a ___________ cellular response. ________ soluble hormones bind to cell surface receptors and ______ soluble hormones bind to intracellular receptors.

A
Picomolar
Binding
Target
Specific
Water 
Lipid
61
Q

How do water soluble hormones exert effects after binding to extracellular receptors?

A

GPCRs -dissociation of alpha subunit, activate effector, 2nd messenger formed, activate protein kinase, phosphorylate target proteins for cellular response OR tyrosine kinase - dimerisation (not insulin), autophosphorylation of some tyrosines, recruit adaptor proteins and signalling complex to activate PK to phosphorylate target proteins for a cellular response.

62
Q

How do lipid soluble hormones exert effects after binding to intracellular receptors?

A

They diffuse across the plasma membrane and may bind to a cytoplasmic receptor to become a complex or solely enter the nucleus to bind to the HRE (hormone response element) in some promoter regions, leading to the expression of a new protein which mediates the hormonal effect.

63
Q

Obesity epidemic - chronic imbalance of energy intake and ___________. A BMI>____ kg/m(2). If intake exceeds î then energy _______ increase - _____ in adipose tissue, with the opposite having the effect of __________.

A
Expenditure
30
Stores
TAG
Depletion
64
Q

Where is appetite control/satiety controlled?

A

A centre in the hypothalamus called the Arcuate nucleus (clusters of neutrons are known as nuclei) is mainly involved.

65
Q

In the Arcuate nucleus, what do primary neurones do?

A

Primary neurones process neuronal, Nutrient and hormonal signals.

66
Q

What are the 2 types of primary nucleus is the Arcuate nucleus and what do they do?

A

Stimulators neurones contain neuropeptide Y (NPY) and Agonti-related peptide (AgRP), which promote hunger.
Inhibitory neurones have propiomelancortin (POMC), which yields neurotransmitters including alpha-MSH and beta-endorphin, which promote satiety.

67
Q

What’s the connection between primary and secondary neurones in the Arcuate nucleus?

A

Primary neurones synapse with secondary synapses in other regions of the hypothalamus, where signals are integrated to alter feeding behaviour.

68
Q

Name 2 hormonal signals from the gut and 3 from the rest of the body, which travel to the hypothalamus to control appetite.

A

Ghrelin and PYY (peptide tyrosine tyrosine) from the stomach and lepton, insulin and amylin from the rest of the body.

69
Q

Ghrelin is a __________ hormone secreted from the stomach wall when it’s ________, stimulating __________ primary neurones in the Arcuate nucleus. Filling of the stomach ________ release.

A

Peptide
Empty
Primary
Inhibits

70
Q

Peptide tyrosine tyrosine (PYY) is a short __________ hormone, released cells of the ______ and the _______ when a person is _____. It inhibits primary ___________ neurones of the __________ nucleus and stimulates ___________ neurones. There’s a __________ PYY response after food intake for ________ humans.

A
Peptide
Ileum
Colon
Fed
Excitory
Arcuate
Inhibitory
Blunted
Obese
71
Q

Leptin is a _________ hormone released by __________, which ________ inhibitory and ___________ excitory neurones in the Arcuate nucleus, but also induces expression of ______________ proteins in the mitochondria, so more energy is lost as ______.

A
Peptide
Adiocytes
Stimulates
Inhibits
Uncoupling
Heat
72
Q

What effect does insulin have on the control of appetite?

A

Insulin has a minimal effect; it suppresses the appetite by a similar mechanism to leptin.

73
Q

How is Amylin similar to insulin and what else can it do?

A

Amylin is a peptide hormone also released from the beta cells of the pancreas, which suppresses the appetite, but it also decreases glucagon secretion and incites slow gastric emptying.

74
Q

What is Pramlintide?

A

Pramlintide is an analogue of Amylin, which is used to treat type 2 diabetes.

75
Q

Who responds well to leptin injections?

A

Those with a loss of function in the leptin gene, leading to obesity - there is little effect with ‘common obesity’.

76
Q

Overall, in which different ways is the appetite controlled?

A

Control is orexigenic (appetite stimulation) or anorexigenic, as well as hedonistic inputs involved.