Lecture 5 Flashcards by Ava Randall

What is haemopoiesis and where does it occur in adults/infants/embryo?

Production of blood cells.
In adult it is concentrated in the axial skeleton (pelvis, sternum, skull, ribs, vertebrae)
It is extensive throughout infants. (Lots of active haemopoietic tissue)
In yolk sac of the embryo, then in the liver/spleen then moves to bone marrow.

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What is a trephine biopsy used for?

Extract and view liquid bone marrow.

-needle into back of pelvis, superior iliac crest

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What are the lineage pathways arising from haemopoietic stem cells?

Hematopoietic stem cell differentiates into a common myeloid progenitor (produces cells for clotting i.e. megakaryocyte>platelets, erythrocytes, myeloblast-WBC’s: basophils, neutrophils, eosinophils, monocytes> macrophages), or a common lymphoid progenitor (produces lymphocytes)

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What determines what each progenitor is going to develop into?

-Transcription factors
-interaction with non-haemopoietic cells e.g. endothelial cells
-hormones
Erythropoietin: for development of RBC’s, secreted by kidney, stimulated when oxygen levels are low due to lack of RBC’s
Thrombopoietin: produced by liver/kidney regulating the production of platelets (megakaryocytes)

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What are special about HPSC’c?

capable of self-renewal
differentiate into variety of specialised cells
not expect to see any in peripheral blood, only the bone marrow so if you do see myeloblasts in the blood there is a problem with haematopoiesis

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What are HPSC’s used for?

can be removed before chemotherapy (which would normally kill off the bone marrow), freeze them, and then reintroduced after
collect stem cells from the umbilical chord

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What is the main cells in the reticuloendothelial system?

Part of immune system

monocytes
macrophages (phagocytic cells)
remove dead/ damaged cells and identify and destroy forgien antigens
main organs are spleen (red pulp macrophage) and liver (Kupffer cell)

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Different pulp functions of the spleen:

Red pulp: RBC’s go through here, lots of sinusoids lined by endothelial macrophages

White pulp: lymphocytes here (look like follicles) (forgein antigen shown here to start immune response)

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Functions of the spleen?

monitors circulating cells and removing damaged/dead/old cells
sequestration and phagocytosis
pooling for cells that need to ‘rest’, so if we need them RBC’s to ensure we don’t become hypotensive /WBC’s exit to fight infection
extramedullary haematopoiesis (if bone marrow is stressed, it occurs in the spleen, pluripotent stem cells proliferate)
blood pooling platelets/RBC’s readily mobilised during bleeding (spleen expands in size)
1/4 of T cells, 15% B cells stay in spleen

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Blood supply to spleen:

Splenic artery

White cells and plasma pass through the white pulp

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Why would the spleen be larger? (Splenomegaly)

liver disease (fibrosis so hard for blood to pass through liver): blood that backs up in splenic artery leading to a large spleen (portal hypertension)
disorder of RBC’s/immune problems
expanded by infiltration of cancer cells/microbes
reverting to it being site of haematopoiesis

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How do you examine the spleen?

Not normal for it to be large

start to palpate in Right Iliac Fossa and go upwards, to prevent missing the spleen
breathe in and out (as breathe in spleen will hit your hand)

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What is splenoomegaly and its consequences?

Enlarged spleen
Consequences:
-more blood volume can sit in spleen, so patients blood count will be measured as low as circulating blood is low
-spleen no longer protected by rib cage so can rupture if exercise

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What is hyposplenism?

-lack of spleen (splenectomy)/low functioning spleen
Causes:
-sickle cell (infarct spleen, blood supply to spleen is cut off, so spleen shrinks)
-GI disease
-autoimmune disorders

(See irregular RBC’s as they aren’t cleared, and you see Howell Joly inclusion bodies with a bit of nucleus inside)

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What are patients at risk of with hyposplenism?

Infection/sepsis from encapsulated bacteria.
E.g. streptococcus pneumonia, haemophilus influenzae, meningococcus
-patients must be immunised and given lifelong antibiotics

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What is the MCV?

How large the RBC’s are (helps to define some abnormalities seen in patients)
Mean corpuscular volume
(80-100fl)

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What is the shape of RBC?

Biconcave disc (8 micrometers diameter)

flexible and uniform (no nucleus/mitochondria)
high SA:V ratio, high area for gas exchange
lifespan of 120 days

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Functions of RBC’s?

deliver oxygen to tissues (carry Hb, and maintain it in reduced i.e. ferrous state)
have systems inside to produce ATP to maintain Hb in reduced state so oxygen can bind to it

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Structure of Hb?

-tetramer of 2 pairs of globin chains, each with own haem molecule which contains iron (2 alpha, 2 beta)
-exists in 2 configurations (bound/unbound to oxygen)
(globin gene on chromosomes 11 and 16)
(Switch from fetal to adult Hb at 3-6 month)

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What is the RBC membrane structure?

-flexible (can flex in half to fit through a gap and not get damaged)
-bilipid membrane
(Changes to plasma membrane can make them less flexible so more fragile and break-Haemolytic anaemia, lifespan of RBC’s not 120 days)

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How is haem degredated? (At 120 days/if damaged)

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identified by macrophages in RES, broken down (globin chains are recycled, haem is removed and iron is recycled)
haem circulates as bilirubin in blood to liver (unconjugated-yellow, carried in blood attached to albumin)
in liver conjugated with glucoronic acids (conjugated bilirubin)
secreted in bile into duodenum
in duodenum the glucaronic acid is removed by bacteria
bilirubin>urobilinogen>stercobilin

What is cytopenia?

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Reduction in number of blood cells

Function of neutrophil

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Phagocytose and degrade with their granules which contain enzymes
(Lobed structure )
-live for 4 days

What is the maturation of neutrophils stimulated by?

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Hormone G-CSF (glycoprotein growth factor and cytokine)

produced by damaged endothelial cells, macrophages
increases production of neutrophils
increase speed of neutrophil maturation
enhances chemotaxis
enhances phagocytosis/killing of pathogens

What is neutrophilia and causes?

Increase in number of circulating neutrophils - acute haemorrhage (marginated pool of neutrophils stick to membrane, in haemorrhage these are released from side of the vessels so neutrophil count increases) - infection - myeloproliferative disorder - cancer - tissue damage - smoking - drugs - cytokines (G-CSF) - acute inflammation - metabolic/endocrine disorders

What is neutropenia and the causes?

``` Low neutrophil count. -life threatening bacterial/fungal infections can occur -mouth ulcers Causes: Reduced production Increased removal/use ```

What is a medical emergency to do with neutropenia?

Neutropenic sepsis | -give intravenous antibiotics immediately

What are monocytes and monocytosis?

-largest cell in blood usually -once in tissues from blood they develop into macrophages -phagocytose bacteria and present proteins to stimulate immune response Monocytosis: -increased number of monocytes Causes: -bacterial infection -inflammatory conditions -carcinoma -myeloproliferative disorders -leukaemia

What are eosinophils?

- phagocytosis - have large orange granules full of enzymes (cytotoxic proteins) - responsible for immune response against multicellular organisms (helminths) - mediators of allergic responses

Causes of eosinophilia?

``` Common: -allergic disease (asthma, eczema) -drug hypersensitivity -skin diseases -parasitic infection -Chung-strauss (rare autoimmune disease resulting in inflammation of small vessels) Rare -Lymphoma -leukaemia -idiopathic hypereosinophilic syndrome -myeloproliferative conditions ```

What are basophils?

- contain granules with enzymes - least common - important in allergic reactions and inflammatory conditions - granules stain deep blue so mask nucleus

Causes of basophilia:

``` Reactive -hypersensitivity reactions -ulcerative collitis -rheumatoid arthritis Myeloproliferative conditions ```

What are lymphocytes?

Originate in bone marrow- from common lymphoid progenitor | -produce T(cellular immunity)/B-Ab production (humoral immunity)/NK cells (cel mediated cytotoxicity)

What is lymphocytosis?

- viral infections (often in children) - bacterial infection - stress related (MI) - post splenectomy, as they usually pool in spleen - smoking - lymphoproliferative disorders (lymphomas)

Where do you usually see damage to the bones in adults?

Axial skeleton where there is active haematopoiesis occurring e.g. cancer of bone marrow cells

What is the reticuloendothelial system? (RES)

- monitoring & removing bone marrow cells | - main cell type is monocytes (when circulating the blood)/macrophages (once entered the tissue)

Where is the spleen located?

Left side of your body (left hand side) | liver & heart lie on the right

In what conditions do you see extramedullary haematopoiesis?

- myelofibrosis (Cancer of bone marrow: fibrosis in marrow so not enough room for normal cells to develop) - thalassaemia

How can we tell if a patient is hyposplenic?

-not cleaning out RBC’s -few irregular RBC’s on blood film -irregular blood cells with fragments of nucleus left in them (Howell Jolly Bodies) (RBC’s containing these inclusion bodies would be normally removed by fully functioning spleen)

What is RBC?

Red Blood Count- how many RBC’s in given volume | 4.4-5.9 x 10^12/l

Why measure Hb?

Tells you how effective the RBC’s are

What do RBC’s lack?

No nucleus | No mitochondria

Are there many types of globin chains?

Yes. Different globin chains combine to produce different Hb’s with different properties. E.g. fetal Hb- switch from this to adult at 3-6 months

Where are the genes for globin genes?

Chromosome 11 & 16

Why can RBC’s be the wrong shape?

-hereditary e.g. spherocytosis- forming spherocytes (spheres)

What causes jaundice?

Excess bilirubin transported in blood e.g. from haemolytic anaemia -yellow sclera

What makes your faeces brown?

Stercobilin

What makes your urine yellow?

- urobilinogen absorbed into blood and transported to the kidney - oxidised to urobilin - urobilin = yellow

What is the suffix for an increase in blood cells?

- cytosis | - philia

What is recombinant G-CSF used for?

-neutropenic patients (can cause neutropenic sepsis if G-CSF isn’t given to increase neutrophil number) E.g. following chemotherapy

Lecture 5 Flashcards

(50 cards)