Haematology In Systemic Disease And Introduction To Endocrine System Flashcards
Explain the common haematological abnormalities that can occur in patients with non-haematological systemic diseases.
In both primary care and hospital settings abnormal blood tests are more like to be due to the patient having a systemic disease. The changes can be seen in:
- Red cells (anaemia + secondary causes of polycythaemia)
- White cells: Count can be raised for many reasons (infection/inflammation) and neutropenia or lymph open is can occur in the setting of systemic disease
- Platelets: Both thrombocytopenia and thrombocytosis are more commonly reactive than primary
- Clotting factors and fibrinogen: Bleeding due to consumption of these factors occurs.
Describe the clinical and haematological features of the anaemia of chronic disease
Anaemia of chronic disease is the 2nd most common cause of anaemia. It is associated with inflammatory conditions e.g., rheumatoid arthritis, chronic infections, and malignancy. Chronic release of cytokines increases production of hepcidin by the liver. Increased hepcidin results in less iron absorption in the gut and less release of iron from stores, by decreasing ferroportin expression and promoting internalisation of ferroportin molecules.
It can therefore be seen as a functional loss of iron
Explain how anaemia of chronic disease can be distinguished from iron deficiency.
Iron deficiency anaemia is an anaemia caused by low iron stores in the body. Anaemia of chronic disease however, is a functional anaemia of iron restricted erythropoiesis related to diseases such as infections, autoimmune diseases, cancer and end-organ failure.
In both conditions, serum iron level is low, small or microcytic cells can be present, and transferrin is elevated in iron-deficiency anemia
Describe the common causes and clinical significance of neutropenia, neutrophilia, lymphocytosis and eosinophilia
Neutrophilia (high neutrophil count) - Bacterial infection. Worsening neutrophilia could represent the development of an infective complication
Neutropenia (low neutrophil count) - Post viral infection. Patients receiving chemotherapy may need blood support and are at risk of neutropenic sepsis
Lymphocytosis (High lymphocyte count) - Viral infection in children e.g., Bordatella Pertussis
Eosinophilia (High eosinophil count) - Parasitic infection
Describe the man features of control systems in the body.
There are some key features which are common to all control systems:
- Communication: There must be communication between the different components for a control system to operate.
- Control centre: Role is to determine the reference set point, to analyse the afferent input and to determine the appropriate response.
- Receptor: Sensors are required to detect stimuli such as changes in the environment.
- Effector - Effectors are agents that cause change. The control centre produces an output which is communicated via efferent pathways to effectors.
- Feedback: In feedback, the output (effect) has an effect on the control centre.
What are the haematological conditions associated with chronic kidney disease
Patients with chronic kidney disease typically develop normochromic normocytic anaemia (severity is proportional to severity of kidney disease). The lower the glomerular filtration rate, the higher the severity of anaemia.
Deficiency of erythropoietin is the most dominant underlying cause for anaemia development. Lower levels of erythropoietin in circulation leads to lower levels in bone marrow and insufficient red cell production.
Damaged kidneys reduced renal clearance of hepcidin which along with associated increase in hepcidin production, reduce erythropoiesis due to a function lack of iron in chronic kidney disease.
What are the haematological conditions associated with Rheumatoid Arthritis
Rheumatoid arthritis have abnormalities in blood results full explained by the multi system disease.
The anaemia of chronic disease is proportional to the severity of disease. Coexisting iron deficiency occurs more commonly due to the needs of NSAIDs and corticosteroids which cause gastrointestinal blood loss. In flares, neutrophilia and thrombocytosis may be present.
Felts syndrome is the triad of Rheumatoid arthritis, splenomegaly and neutropenia
What are the haematological conditions associated with Alcholism
Chronic alcohol consumption has a range of adverse on the marrow, spleen and blood cells. Heavy consumption has a generalised toxic effect on bone marrow leading to suppression of haematopoesis, resulting in production of abnormal blood cell precursors that cannot mature into functional cells. Red cells become macrocytic.
Acetaldehyde produced from ethanol metabolism can produce protein-acetaldehyde adducts leading to an immune response against the modified proteins
Define the term hormone and list the features of communication processes involving hormones
Hormones are chemical messengers that are involved in communication and travel via the bloodstream. They are secreted by endocrine glands and the cells that hormones act on are target cells. Communication processes include:
- Autocrine: Hormone signal acts back on the cell of origin
- Paracrine: Hormone signal carried to adjacent cells over a short distance via interstitial fluid
- Endocrine: Hormone signal released into bloodstream and carried to distant target cells
- Neurocrine: Hormone originates in neurone and after transport down axon released into bloodstream and carried to distant target cells.
List the classes of chemical substances which can act as hormones
Peptide/polypeptide hormones - Largest group made up of short or long chains of amino acids, e.g., insulin, glucagon, growth hormone, placental lactogen.
Glycoprotein hormones - Large protein molecules with carbohydrate side chains e.g., LH, FSH, TSH which are secreted by the anterior pituitary gland.
Amino acid derivatives (amines) - Small molecules synthesised from amino acids e.g., adrenaline, and the thyroid hormones - thyroxine and trilosothyronine
Steroid hormones - Derived from cholesterol e.g., cortisol, aldosterone, testosterone and oestrogen
Describe how hormones are transported
Polypeptide hormones, glycoprotein hormones and adrenaline are relatively hydrophilic and are transported in the bloodstream dissolved in the plasma. Steroid hormones and thyroid hormones are relatively hydrophobic and need specialised transport proteins
Often specific proteins e.g., thyroid hormones (thyroxine-binding globulin, TBG).
The roles of the carrier proteins is to increase solubility of hormone in plasma, increase half life and as a readily accessible reserve.
How do hormones act upon target cells
Hormones exert their effects by binding to specific receptors. Target cells express specific receptor for hormone so specific cellular response is to hormone, whilst non-target cells have no receptor so there is no response.
Water soluble hormones bind to cell surface receptors:
- G protein coupled receptor e.g. Adrenaline receptor
- Tyrosine kinase e.g., insulin receptor.
Lipid soluble hormone bind to intracellular receptors:
- Type 1: Cytoplasmic receptor binds hormone and receptor complex, enters nucleus and binds to DNA
- Type 2 0 Hormone enters nucleus and binds to pre-bound receptor on DNA. Binding relievers repression of gene transcription
Explain the ways in which hormone secretion may be controlled
The rate of secretion of a hormone is usually controlled by negative feedback. Hormones are constantly lost from the circulation so the secretion rate must be adjusted to maintain an appropriate blood concentration.
Discuss examples of biological rhythms
Rather than the set point being a fixed steady value, it can vary over time giving rise to biological rhythms. For example:
- Levels of cortisol in the blood varies during the day (peak at 7am to a through at 7pm). Therefore time should be noted when taking a sample of blood for cortisol.
- The menstrual cycle is an example and core body temperature varies during the cycle. A sudden increase in core body temperature can be used as a marker of ovulation.
Describe in outline the control of appetite
The appetite control centre is located in the hypothalamus. The arcuate nucleus within the hypothalamus plays a central role and contains primary neurones that sense metabolite and hormone levels. There are two types of primary neurone:
- Stimulatory neurones contain neuropeptide Y (NPY) and Agouti-related peptide (AgRP). These promote hunger.
- Inhibitory neurone contain pro-opiomelanocortin (POMC) which yields several neurotransmitters including alpha MSH and beta endorphin. Thiese promote satiety.
Primary neurones synapse with secondary neurones in other regions of hypothalamus and the signals integrated to alter feeding behaviour.
