Causes of anaemia AND iron metabolism and anaemia

Question 1

What is anaemia?

Answer 1

less than normal/adequate circulating functional haemoglobin

Question 2

Outcomes of Vit B12 deficiency

Answer 2

1 impaired DNA synthesis
2 impaired fatty acid metabolism
3 neurological disorders

Question 3

Predisposing factors to gastric cancer (3 categories and examples)

Answer 3

1 Environmental
- H pylori
- diet
- low SES
- smoking

2 Host
- chronic gastritis (autoimmune, intestinal metaplasia)
- partial gastrectomy
- gastric adenomas
- Barrett’s eosophagus

3 Genetic
- slight increased risk with group A
- FHx genetic carcinoma
- hereditary nonpolyposis colon cancer syndrome
- familial gastric carcinoma syndrome (E cadharin mutation, increased risk of lobular breast cancer)

Question 4

Anaemia: classification by morphology (3)

Answer 4

1 microcytic hypochromic anaemia
2 megaloblastic anaemia
3 normochromic normocytic anaemia

Question 5

Complications of chronic peptic ulcer

Answer 5

1 penetration (ulcer base formed by pancreas, omentum, liver)
2 perforation (peritoneal cavity)
3 haemorrhage
4 fibrosis (obstruction / deformity)
5 carcinoma (very rare)

Question 6

Serum ferritin in determining iron status?

Answer 6

serum ferritin = good indicator of iron stores in normal conditions

ferritin is an acute phase reactive protein, and its serum concentrations can be elevated, irrespective, of change in iron stores, by inflammation or infection

Question 7

What is pernicious anaemia? What does it cause (histological features)? functional result?

Answer 7

immunologically mediated autoimmune attack glands of gastric fundic/body mucosa

intrinsic factor secreting cell mass decreased = Vit B12 stores become depleted = anaemia

impaired rbc productuion = megaloblastic

Question 8

Gastric neuroendocrine tumour (carcinoid):
- what cells are typically involved?
- underlying conditions? (3)
- what state causes ECL hyperplasia?

Answer 8

ECL cells

1 chronic atrophic gastritis
2 multiple endocrine neoplasia type 1 (MEN 1)
3 Zollinger-Ellison syndrome

Hypergastrinaemic state

Question 9

List types of tumours of the stomach that could lead to anaemia (7)

Answer 9

1 non neoplastic polyps
2 adenomas
3 adenocarcinomas (90-95% tumours)
4 lymphoma
5 GIT stromal tumours
6 neuroendocrine tumours
7 metastatic tumours

Question 10

Outcomes of folate deficiency (4)

Answer 10

1 impaired DNA synthesis
2 megoblastic anaemia
3 neural tube defects of new born
4 increased risk of CVD

Question 11

What is hemosiderin?

Answer 11

Iron storage complex that less readily releases iron for body needs. Stored in liver and heart.

Question 12

Define haematinic

Answer 12

a substance that improves the quality of blood by increasing hbg production or by increasing RBC number

Question 13

What are oxyntic glands?

Answer 13

Located in gastric fundic/body mucosa

Stomach glands that secrete HCl and IF (parietal cells)

proteolytic enzymes (chief cells)

histamine (endocrine cells)

Question 14

GIT stromal tumour (GIST):
- define
- cells and function
- pathophysiology
- genes (2), type of mutation and at what exon usually

Answer 14

Specific KIT or platelet-derived growth factor receptor alpha (PDGFRA) mutation driven mesenchymal tumour.

A growth of cells formed from Interstitial cajal cells (ICC) - nerve cells - which are pacemakers of the gut.

c-kit (CD117) = role in cell growth, survival and migration
- GOF mutation
- exon 11

PDGFRA = proteins
- abnormal protein production
- exon 18

Question 15

Hyperplastic gastric polyps:
- synonyms (2)
- common underlying condition and pathophysiology
- characteristics

Answer 15

1 inflammatory polyps
2 regenerative polyps

Chronic gastritis: mucosal injury and healing –> polypoid foveolar hyperplasia –> hyperplastic polyp

Architecturally distorted, irregular, cystically dilated and elongated foveolae, “corkscrew” glands

Dysplasia incidence 1-20% (related to size)

Question 16

List haematinics

Answer 16

Iron
B12
Folate

Question 17

Haemoglobin: structure, iron absorption, role B12/folate,

Answer 17

Haem: protoporphyrin + Fe
Globin: alpha and beta chains

Iron - dietary nonhaem exposed to HCl –> Fe2+/ferrous iron and is absorbed in duodenum

Required for DNA synthesis in reticulocytes to survive until mature RBC
- deficiency will lead to immature or macrocytic RBC with poor quality haemoglobin

Question 18

List non neoplastic polyps (4)

Answer 18

1 hyperplastic polyps
2 inflammatory fibroid polyps
3 hamartomatous polyps (fundic gland, peutz-jeghers, juvenile)
4 embryonic rests and heterotopias

Question 19

Iron…
- transferrin
- ferritin
- lactoferrin
- redox-enzymes
- iron-sulphur enzymes

Answer 19

Transferrin - plasma Fe transport
Ferritin - cellular Fe storage
Lactoferrin - binds Fe in milk
Redox enzymes - iron at active site (electron transport)
Iron-sulphur proteins - ferroredoxins (electron transport)

Question 20

1 Iron absorption: haema vs non haeme

2 Iron transport out of cell

3 what blocks iron absorption?

Answer 20

1
Heme iron: heme transporter
Non-heme: Fe3+ –> Fe2+ by duodenal cytochrome B. DMT1 transporter

2 Ferroportin transports Fe2+ out of cell
- Hephaestin converts Fe2+ to Fe3+
- Transferrin transports Fe3+

3 hepcidin: ferroportin degredation

Question 21

Describe the metastatic spread of gastric carcinomas in terms of location? (5)

Answer 21

1 Supracalvicular node (Virchow’s) can be first presenation

2 periumbilical region –> subcutaneous nodule (sister Mary Joseph nodule)

3 local invasion: pancreas, duodenum, retroperitoneum

4 widespread: peritoneal seeding, liver and lungs

5 ovaries (Krukenberg tumour): metastises from breast, pancreas and gallbladder can also go to ovaries

Question 22

Pathology of stomach: 4 conditions

Answer 22

1 actue gastritis
2 chronic gastritis
3 ulcers
4 tumours of the stomach

Question 23

Microscopic subtypes of gastric adenocarcinomas (2)

Answer 23

1 glandular type - papillary, tubular, mucinous
- malignant glands infiltrating into deeper parts of the wall

2 diffuse or signet ring cell carcinoma
- single cells diffusely infiltrating into the wall

Question 24

Clinical features of peptic ulcers (6)

Answer 24

1 epigastric gnawing, burning or aching pain
2 may present with complications such as:
- iron deficiency anaemia
- frank haemorrhage
- perforation
3 pain usually worse at night and occurs 1-3 hours post prandial
5 nausea, vomiting, bloating, belching, and significant weight loss
6 penetrating ulcers lead to referred back pain (back, LUQ, chest)

Question 25

How anaemia manifests symtomatically depends on...?

Answer 25

Rate - slowly: body tissues gradually compensate for decreasing O2 supply - quickly: basically go into shock Overall health - co morbidities: if one system is compromised, that system manifests effects of ischaemia first

Question 26

3 ways to estimate iron level?

Answer 26

1 total iron 2 total iron binding capacity 3 percentage transferrin saturation

Question 27

Underlying pathophysiology of iron deficiency anaemia

Answer 27

1 dietary lack of iron - infants, children, poor, elderly 2 impaired absorption - sprue, chronic diarrhoea, post-gastrectomy (decreased acid and rapid duodenal transit), dietary inhibitors e.g. oxalates) 3 increased requirement - children, adolescents, premenopausal and pregnant women 4 chronic blood loss - peptic ulcers, haemorrhagic gastritis, gastric cancer

Question 28

Anaemia: classification by mechanism (3)

Answer 28

1 Blood loss - acute and chronic 2 increased rate of haemolysis - intrinsic red cell abnormalities (haemoglobinopathies, cell membrane disorders, red cell enzyme deficiencies) - extrinsic damage to red cells (antibody mediated, traumatic, infections, chemical injury, hypersplenism) 3 impaired RBC production - megaloblastic anaemia - iron deficiency - anaemia of chronic infections, bone marrow infiltrates

Question 29

What glands are in gastric antral mucosa?

Answer 29

endocrine cells: gastrin enterochromaffin cells - D cells: somatostatin - X cells: endothelin

Question 30

pH and oxidation/reduction of Fe3+/Fe2+ (4)

Answer 30

1 non heme iron (plant foods) largely exists in ferric form = Fe3+ 2 At physiological pH, Fe2+ is rapidly oxidised to Fe3+ which is insoluble 3 gastric lowers the pH in proximal duodenum reducing Fe3+ in intestinal lumen by ferric reductases - to allow transport of Fe2+ across the mucosa 4 when gastric acid production is impaired (for instance by a drug), iron absorption is reduced

Question 31

2 main types of gastric lymphomas

Answer 31

1 gastric marginal zone B cell lymphoma 2 gastric diffuse large B cell lymphoma

Question 32

Causes of chronic gastritis (5) leading to anaemia

Answer 32

1 autoimmune gastritis (anti parietal cell and anti IF antibodies and IF deficiency) 2 Helicobacter Pylori infection 3 Reflux/reactive/chemical gastropathy 4 Granulomatous (e.g. Crohn's) 5 Others (lymphocytic gastritis, graft-versus-host disease, amyloidosis, radiation, toxic [alcohol, smoking])

Question 33

Gastric ulcers as a cause of anaemia: - define - acute ulceration: causes, morphology - chronic ulceration: causes, morphology - morphology of neoplastic ulcer

Answer 33

A local defect or discontinuity in the epithelial lining of the stomach; an area of complete loss of the mucosa penetrating at least to the level of the submucosa. Acute - NSAIDs, stress (shock, burns, sepsis, trauma), intracranial injury (traumatic, post-surgery) - usually < 1cm and multiple, anywhere in the stomach Chronic - sharply perpendicular walls, smooth base, minimal elevation of marginal mucosa, rugal folds radiate from margin of ulcer - usually solitary, < 4cm Neoplastic - bowl-shaped, shallow with sloping edges, granular marginal mucosa; rugae terminate short of the ulcer margin because of infiltrate)

Question 34

Why would there be less circulating functional haemoglobin? (3)

Answer 34

Blood loss Increased rate RBC breakdown Impaired RBC production

Question 35

Causes of acute gastritis (4) leading to anaemia

Answer 35

1 acute haemorrhagic erosive gastritis (stress gastritis: sepsis, burns, ehad injury) 2 NSAIDs/aspirin (acute haemorrhagic gastritis, acute erosions and reactive gastropathy) 3 Alcohol (subepithelial haemorrhage, mucosal edema) 4 Others (chemotherapy, iron pill gastritis, acute corrosive gastritis, ischaemic gastritis, radiation gastritis, viral (CMV), bacterial (salmonella))

Question 36

Classic picture of iron deficiency anaemia? Timeline?

Answer 36

Microcytic and hypochromic (advanced iron deficiency!) Iron deficiency (not advanced) = normocytic and normochromic