Session 6 ILOs - Haematological changes in chronic disease and introduction to endocrine system and appetite

Question 1

Explain the common haematological abnormalities that can occur in patients with non-haematological systemic diseases

Answer 1

1. Chronic kidney disease
   - Anaemia, secondary polycytheaemia, neutropenia, neutrophilia, thrombocytopenia
2. Rheumatoid Arthritis
   - Anaemia is multifactorial
   - High platelets and neutrophils when the disease is active (CRP also up)
   - But low platelets and neutrophils may occur during treatment, autoimmune reactions or hypersplenism (as splenomegaly may occur in RA)
   - Neutropenia in Felty’s syndrome
3. Alcoholism/liver damage
   - Portal hypertension can because splenomegaly
   - Thrombocytopenia (as thrombopoietin is made in liver and splenic pooling)
   - See target cells due to increase cholesterol to phospholipid ratio
   - Can be deficient in clotting factors (made in liver)
4. Post-operative reactive changes
   - Anaemia, temporary relative polycytheaemia, neutropenia, neutrophilia, thrombocytopenia, thrombocytosis (similar to chronic kidney disease)
5. Cancer
   - Anaemia, polycytheaemia, neutropenia, neutrophilia, thrombocytopenia, thrombocytosis (similar again!)

Question 2

Describe the clinical and haematological features of the anaemia of chronic disease and explain how this is distinguished from iron deficiency

Answer 2

Anaemia of chronic disease has 3 contributors - all caused by inflammatory cytokines

1. Iron dysregulation
2. Lack of response of bone marrow to erythropoietin
3. Reduced lifespan of RBC (due to abnormality)

Anaemia of chronic disease is a ‘functional’ iron deficiency, where there is sufficient iron available but it is not made available to developing RBC. Hepcidin is regulated by inflammatory cytokines and high inflammatory cytokines prevents iron absorption from the gut AND iron release from macrophages to the RBCs

Question 3

Describe the common causes and clinical significance of neutropenia, neutrophilia, lymphocytosis and eosinophilia

Answer 3

Neutrophilia is often associated with bacterial infections

Neutropenia is often associated with severe bacterial infections or sepsis (due to neutrophils being used up)

Lymphocytosis is often associated with viral infections (also with neutropenia)

Eosinophilia is often associated with parasitic infections

Question 4

Describe the main features of control systems in the body

Answer 4

Initial stimulus, detected by a receptor, which then communicates to the control centre through an afferent pathway

The control centre feeds back to the effector organs/glands via the efferent pathway and causes negative feedback on the stimulus

Communication pathways can be through either the nervous system (action potentials) or the endocrine system (hormones)

Question 5

Discuss examples of biological rhythms

Answer 5

Circadian (diurnal) rhythms:

• Core body temperature
• Cortisol
• Melatonin

Question 6

Define the term ‘hormone’ and list the features of communication processes involving hormones (e.g. autocrine)

Answer 6

Hormones are chemical signals produced in endocrine glands or tissues, that travel in the bloodstream to cause an effect on distant tissues

1. Autocrine
2. Paracrine
3. Endocrine
4. Neurocrine

Question 7

List the classes of chemical substances which can act as hormones

Answer 7

1. Peptide/polypeptide hormones
   - Water soluble
   e. g. insulin and glucagon
2. Amino acid derivative hormones
   - Water soluble and lipid soluble
   e. g. adrenaline and noradrenaline
3. Glycoprotein hormones
   - Water soluble
   e. g. LH, FSH
4. Steriod hormones
   - Lipid soluble
   e. g. aldosterone, testosterone

Question 8

Describe how hormones are transported and act upon target cells

Answer 8

Hormones travel in the blood - either free or bound

Free: peptides and adrenaline
Bound: most other hormones! Usually carriers are specific to the hormone

Key: only free form is biologically active

For a hormone to act on a target cell, it must have receptors to the hormone (also some regulation for lipid soluble hormones)

Water soluble: use of G-protein coupled receptors or tyrosine kinase receptor
Lipid soluble: type 1 (involves cytoplasmic receptor) and type 2 (directly enters the nucleus)

Question 9

Explain, in general terms, the ways in which hormone secretion may be controlled.

Answer 9

1. Rate of hormone production
2. Rate of hormone delivery
3. Rate of hormone degradation

Question 10

Describe in outline the control of appetite

Answer 10

The appetite control centre is located in the hypothalamus and contains arcuate nuclei

The primary neurones in the acute nucleus process the neuronal, nutrient and hormonal signals from the blood. These primary neurones can be stimulatory (neuropeptide Y and Agouti-related peptide) which promote hunger, or can be inhibitory (POMC) which promote fullness

The primary neurones synapse with secondary neurones in other regions of the hypothalamus and the signals are integrated to modulate feeding behaviour (appetite).

Question 11

Discuss the hormones involved in the control of appetite

Answer 11

2 types:

1. Hormones from gut -> hypothalamus
   Ghrelin - released from stomach wall when empty and stimulates appetite
   PYY (peptide tyrosine tyrosine) - released from cells in ileum and colon in response to feeding and inhibits appetite
2. Hormones from body -> hypothalamus
   Leptin - released by adipocytes and suppresses appetite
   Insulin - suppresses appetite in a similar way to leptin
   Amylin - secreted by beta cells in pancreas and suppresses appetite