Causes of anaemia AND iron metabolism and anaemia Flashcards
What is anaemia?
less than normal/adequate circulating functional haemoglobin
Outcomes of Vit B12 deficiency
1 impaired DNA synthesis
2 impaired fatty acid metabolism
3 neurological disorders
Predisposing factors to gastric cancer (3 categories and examples)
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)
Anaemia: classification by morphology (3)
1 microcytic hypochromic anaemia
2 megaloblastic anaemia
3 normochromic normocytic anaemia
Complications of chronic peptic ulcer
1 penetration (ulcer base formed by pancreas, omentum, liver)
2 perforation (peritoneal cavity)
3 haemorrhage
4 fibrosis (obstruction / deformity)
5 carcinoma (very rare)
Serum ferritin in determining iron status?
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
What is pernicious anaemia? What does it cause (histological features)? functional result?
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
Gastric neuroendocrine tumour (carcinoid):
- what cells are typically involved?
- underlying conditions? (3)
- what state causes ECL hyperplasia?
ECL cells
1 chronic atrophic gastritis
2 multiple endocrine neoplasia type 1 (MEN 1)
3 Zollinger-Ellison syndrome
Hypergastrinaemic state
List types of tumours of the stomach that could lead to anaemia (7)
1 non neoplastic polyps
2 adenomas
3 adenocarcinomas (90-95% tumours)
4 lymphoma
5 GIT stromal tumours
6 neuroendocrine tumours
7 metastatic tumours
Outcomes of folate deficiency (4)
1 impaired DNA synthesis
2 megoblastic anaemia
3 neural tube defects of new born
4 increased risk of CVD
What is hemosiderin?
Iron storage complex that less readily releases iron for body needs. Stored in liver and heart.
Define haematinic
a substance that improves the quality of blood by increasing hbg production or by increasing RBC number
What are oxyntic glands?
Located in gastric fundic/body mucosa
Stomach glands that secrete HCl and IF (parietal cells)
proteolytic enzymes (chief cells)
histamine (endocrine cells)
GIT stromal tumour (GIST):
- define
- cells and function
- pathophysiology
- genes (2), type of mutation and at what exon usually
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
Hyperplastic gastric polyps:
- synonyms (2)
- common underlying condition and pathophysiology
- characteristics
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)
List haematinics
Iron
B12
Folate
Haemoglobin: structure, iron absorption, role B12/folate,
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
List non neoplastic polyps (4)
1 hyperplastic polyps
2 inflammatory fibroid polyps
3 hamartomatous polyps (fundic gland, peutz-jeghers, juvenile)
4 embryonic rests and heterotopias
Iron…
- transferrin
- ferritin
- lactoferrin
- redox-enzymes
- iron-sulphur enzymes
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)
1 Iron absorption: haema vs non haeme
2 Iron transport out of cell
3 what blocks iron absorption?
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
Describe the metastatic spread of gastric carcinomas in terms of location? (5)
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
Pathology of stomach: 4 conditions
1 actue gastritis
2 chronic gastritis
3 ulcers
4 tumours of the stomach
Microscopic subtypes of gastric adenocarcinomas (2)
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
Clinical features of peptic ulcers (6)
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)
How anaemia manifests symtomatically depends on…?
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
3 ways to estimate iron level?
1 total iron
2 total iron binding capacity
3 percentage transferrin saturation
Underlying pathophysiology of iron deficiency anaemia
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
Anaemia: classification by mechanism (3)
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
What glands are in gastric antral mucosa?
endocrine cells: gastrin
enterochromaffin cells
- D cells: somatostatin
- X cells: endothelin
pH and oxidation/reduction of Fe3+/Fe2+ (4)
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
2 main types of gastric lymphomas
1 gastric marginal zone B cell lymphoma
2 gastric diffuse large B cell lymphoma
Causes of chronic gastritis (5) leading to anaemia
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])
Gastric ulcers as a cause of anaemia:
- define
- acute ulceration: causes, morphology
- chronic ulceration: causes, morphology
- morphology of neoplastic ulcer
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)
Why would there be less circulating functional haemoglobin? (3)
Blood loss
Increased rate RBC breakdown
Impaired RBC production
Causes of acute gastritis (4) leading to anaemia
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))
Classic picture of iron deficiency anaemia? Timeline?
Microcytic and hypochromic (advanced iron deficiency!)
Iron deficiency (not advanced) = normocytic and normochromic
