Physiology Flashcards
What is the lifespan for red blood cells?
120 days
What is Erythropoiesis?
This is the production of red blood cells (erythrocytes)
What is the nature of vitamin B-12?
Solely ANIMAL BASED
What hormone is the process of Erythropoiesis regulated by?
Erythropoietin
What are the primitive mother cells known as?
Pluripotent Stem Cells
They give rise to Myeloid cells and Lymphoid cells
What is the order of growth for Erythropoiesis?
1.Stem Cell
2.Proerythroblast
3. Early erythroblast
4.Late Erythroblast
5.Normoblast
6.Reticulocyte
7.Erythrocytes
As cells mature the size decreases and their is a loss of nucleus. Nucleus function is replaced by certain enzymes in a fully mature cell. Haemoglobin is now present as cells mature.
What are the necessary requirements for Erythropoiesis?
Iron man - IRON
Fought - FOLATE
Captain - COBALT SALT
America - ANDROGENS
Villans - VITAMIN B 12
” Iron man Fought Captain America Villans”
Where is Erythropoietin produced?
90% - Kidney (Peritubular Interstitial cells)
10%- Liver
What substances stimulate Erythropoietin production?
1.Oxygen Tension in tissues Kidneys
2. Hypoxia Inducible factors ( HIF -1 alpha and beta) under hypoxic conditions.
What is the function of Erythrocytes?
Transport oxygen from lungs to tissues and carbon dioxide from tissues to lungs.
What are the characteristics of Erythrocytes?
- Biconcave, Anucleate
- Contains Haemoglobin
- Contains Lipids, ATP, Carbonic Anhydrase
How long does Erythropoiesis last for?
4-8 days
What is the size of a regular RBC
7-8 microns
What can Plasma Erythropoietin be used to diagnose?
Anaemia- They are high in anaemic persons
Renal disease or Polycythaemia Vera - They are low in persons with this disease.
What is the function of the transcription factor GATA -2 ?
These are involved in initiating erythroid differentiation from Pluripotent cells.
” Gata is too(2) different”
What is the function of transcription factors GATA- 1 and FOG-1 ?
They are important in enhancing the expression of erythroid-specific genes ex globin , haem biosynthetic and red cell membrane proteins.
True or False?
The levels of Erythropoietin are high in persons with Polycythaemia vera and renal diseases?
FALSE!! Levels of Erythropoietin are LOW
True or False?
The levels of Erythropoietin are High in persons with Anaemia or a person with a erythropoietin secreting tumour?
TRUE!!
What is the dominant haemoglobin present in the blood after ages 3-6 months?
Haemoglobin A
Characteristics of Haemoglobin A
Two alpha and two beta chains
Where does Haem synthesis occurs?
In the mitochondria
How long does Leucopoeisis lasts?
10-14 days
What are the functions of Phagocytes?
The function of phagocytes and lymphocytes in protecting the body against infection is closely connected with two soluble protein systems of the body: immunoglobulins and complement.
What is the lifecycle of granulocytes?
4-8 hrs in blood
4-5 days in the tissues
What is the lifespan of monocytes?
10- 20 hrs
What is Aplastic Anaemia?
Aplastic Anaemia is the condition where the body stops producing stem cells
Characteristics of Neutrophils
- 5-6 lobed nucleus
- Specific granules contain leukocyte alkaline phosphatase, myeloperoxidase, hydrolyses,lactoferrin,lysozyme,
- Lifespan in blood is 6-10 hrs
4.First responders cells/ ,most frequent cells - Azurophilic granules (pink-blue in colour) contain proteinases, acid phosphatase, myeloperoxidase, and ~-glucuronidase.
What are the precursors of Neutrophils?
1.Myeoblast
2. Promyelocytes
3.Myelocytes
4.Metamyelocytes
5. Neutrophil
What are the different types of Neutrophils?
Non- Segmented - Immature neutrophils that can be seen in acute infections or inflammation. The bone marrow is sending out everything it has to fight an infection, even if the cells are not fully mature.
Segmented- mature or morphologically appropriate neutrophils with three to five nuclear lobes.
Hypersegmented- neutrophils usually have more than five lobes and are associated with vitamin
B12 or folate deficiencies.
What is the Ferrous state?
Fe2+
What is the Ferric state?
Fe 3+
By what pathway can Red blood cells generate ATP?
By Anaerobic Glycolytic pathway ( Embden-Meyerhof) pathway.
By what pathway can RBC’s produce Glutathione?
By the Hexose monophosphate shunt (pentose phosphate) HMP shunt.
What is the overall process of the Embden-Meyerhof pathway ?
Converts glucose to lactate producing a net production of 2 ATP.
What is the main purpose of Gluthatione produced from the HMP shunt ?
It protects the red blood cells from oxidative stress - eliminating heamolysis.
Where does Haem synthesis occurs?
In the mitochondria.
Where do further Haem synthesis reactions take place?
In the cytoplasm.
Overview of Haem synthesis
- Condensation of glycine and succinyl co-enzyme A under the KEY RATE- LIMITING enzyme δ‐aminolaevulinic acid (ALA) synthase .
2.Further reactions take place in the cytoplasm leading to the formation of protoporphyrin IX - The enzyme ferrochelatase catalyse the insertion of ferrous iron into protoporphyrin IX to form heme
4.This combines with globin chain to form haemoglobin molecule
What are the components of Adult Haemoglobin
2α chains
2β chains
What are the components of foetal haemoglobin?
2α chains
2 gamma chains
What are the clinical uses of erythropoietin?
Anaemia of chronic renal disease
Myelodysplastic syndrome
Anaemia associated with malignancy and chemotherapy
Anaemia of chronic diseases, e.g. rheumatoid arthritis
Anaemia of prematurity
Preoperative uses
What happens when the oxygen molecules are unloaded in a haemoglobin molecules?
When O2 is unloaded the β chains are pulled apart, permitting entry of the metabolite 2,3‐diphosphoglycerate (2,3‐DPG) resulting in a lower affinity of the molecule for O2.
True or false? When there is increased affinity to oxygen , the dissociation curve shifts to the right.
FALSE!! With increased affinity the curve shifts to the LEFT. With a decreased affinity the curve shifts to the RIGHT.
True or False? Faetal haemoglobin doesn’t bind to 2,3 -DPG meaning they give up Oxygen less readily than normal.
TRUE!!
What is Methaemoglobinaemia ( Hb Ms)?
This is a clinical state in which circulating haemoglobin is present with iron in the oxidized (Fe3+) instead of the usual Fe2+ state.
( Fe2+ is the normal state haemoglobin is transferred in)
- It is present in intravascular haemolysis but NOT extravascular haemolysis
What disease has a symptom of cyanosis? ( blue-purple colouring of the skin?
Toxic Methemoglobinaemia. It occurs when a drug or other toxic substance oxidizes haemoglobin.
What is ptosis?
Drooping of the eyes
What is the normal haemoglobin value in men and women?
11.5- 15.5mmHg in Women
15.5- 17.5 mmHg in men
What is a next byproduct of Embden–Meyerhof pathway?
NADPH
What is the purpose of NADPH in this Embder-Meyherhof reaction?
It is needed by the enzyme methaemoglobin reductase to reduce functionally dead methaemoglobin containing ferric iron (produced by oxidation of approximately 3% of haemoglobin each day) to functionally active, reduced haemoglobin containing ferrous ions.
Which shunt produces 2,3 Diphosphoglyceric acid (2,3,DPG) which when bound to Hb, decreases its affinity for Oxygen leading to Oxygen delivery to tissues.
Luebering- Rapaport shunt.
What does a deficiency of pyruvate kinase cause?
Haemolysis of the cell
What process occurs in the HMP shunt?
Approximately 10% of glycolysis occurs by this oxidative pathway in which glucose‐6‐phosphate is converted to 6‐ phosphogluconate and so to ribulose‐5‐phosphate
Where is NADPH also generated?
The HMP shunt. It also produces Glutathione which maintains sulphhydril group (SH) groups intact in the cells and also haemoglobin.
What is as a result glucose‐6‐phosphate dehydrogenase (G6PD) deficiency?
Oxidative stress leading to episodic heamolysis of the cell.
How can oxidative stress arise?
Deficiency of G6PD and Pyruvate kinase
What are Heinz bodies?
These are erythrocyte structures composed of precipitated denatured haemoglobin.
What is the function of pyruvate kinase?
Pyruvate kinase catalyses the conversion of phosphoenol pyruvate to pyruvic acid, generating 2 molecules of ATP.
The ATP generated is used to maintain membrane integrity.
What are the clinical features of pyruvate kinase deficiency?
- Chronic, non- spherocytic haemolytic anaemia
2.Splenomegaly and gall stones
What are gall stones comprised of?
They are comprised of calcium salts of unconjugated bilirubin from the chronic haemolysis.
True of false ?
RBCs cannot compensate for enzyme imperfections and cannot synthesize new enzymes to replace those that become exhausted during the cell’s lifetime.
TRUE!!
What are the enzymes involved in glycolysis?
P PFKM – phosphofructokinase (PFK)
P GK1 – phosphoglycerate kinase (PGK
P - PKLR – pyruvate kinase (PK)
H - HK1 – hexoskinase isoform (HK)
G - GPI – glucose-6-phosphate isomerase (GPI)
“triple P , HG”
What are the enzymes involved in Glutathione metabolism?
G-G6PD – glucose-6-phosphate dehydrogenase
G-GSR- Glutathione reductase
G-GSS- Glutathione synthase
‘Triple G’
What are the enzymes for Purine metabolism?
P - NT5C3A - pyrimidine 5 nucleotidase
A - ADA - Adenosine deaminase
What colour tube has an anticoagulant agent (EDTA) and can be used to identify blood count?
Purple top
What agent does a blue top use and what is tested for?
Trisodium citrate and is used for coagulation
What colour tube is used for molecular studies, cytogenics and lymphocyte count?
Green tube
What stain is used when testing the morphology of blood?
Wright or May- Grunwald -Giemsa stain
How long does it take a reticulocyte to mature
1 day
Where is Iron mainly absorbed?
Duodenum
What is the daily absorption of iron?
1 mg
What is the daily loss of iron for males?
1 mg
What are the factors favouring iron absorption?
- Haem iron
2.Ferrous form (Fe2+) - Acids (Hcl, Vit C)
- Solubilizing agents ( ex sugars, amino acids)
5.Reduced serum hepcidin
6.Ineffective erythropoiesis
7.Pregnancy
8.Hereditary haemochromatosis
What are factors reducing iron absorption?
1.Inorganic iron
2. Ferric form
3. Alkalis- antacids, pancreatic secretions
4. Precipitating agents
5.Increased serum hepcidin
6. Decreased erythropoiesis
7.Inflammation
8. Pytates(wheat, cereal), oxalates(tomato, spinach), carbonates, tannates (tea)
Where is iron normally stored?
Hepatocytes in the liver
What is the differences between inorganic iron and heam iron?
Inorganic iron - This is the iron coming from fruits and vegetables
Haem iron - This is the iron coming from animals ,and meats.
What is the daily loss of iron for females?
1.5 mg
What is a next name for Haemochromatosis?
Bronze diabetes
Where can Hemsosiderin be found?
In the macrophages
What is the soluble form of Iron?
Ferritin
True or False? Hemosiderin is an insoluble form of iron
TRUE!!
What is the name of the protein that is the entrance of iron into the portal plasma?
Ferroportin
What is the name of the protein that allows for iron to exit the cell?
Ferroportin
What is unconjugated billirubin?
This is the bilirubin that cannot leak into urine, it is very large and also binded to a bilirubin binding protein
What are the different evidence of Haemolytic Anaemia?
1.Elevated bilirubin
2.Decreased haptoglobin
3.Elevated LDH
4.Elevated AST
5.Patient has Jaundice( Unconjugated hyperbilirubinemia)
6. Dark faeces
7.Increased reticulocytes
8.Increased urobilinogen in urine
9. Pigmented gallstones
What are the different branches of anemias?
1.Mircrocytic MCV less than 80 fL
2.Normocytic ( Haemolytic & Non hemolytic) 80-100 fL
3.Macrocytic more than 100 fL
At the end of their life cycle, where are red blood cells broken down?
In the macrophages of the reticuloendothelial system
What is the nature of a ferritin molecule?
It contains 22 sub units and a iron-phosphate-hydroxide -core
Describe Haemosiderin ?
- It is an insoluble protein–iron complex of varying composition containing approximately 37% iron by weight.
- It is derived from partial lysosomal digestion of ferritin molecules and is visible in macrophages and other cells by light microscopy after staining by Perls’ (Prussian blue) reaction
What is the name of the copper containing enzyme that catalyses oxidation of the iron TO the ferric form in order to be binded to plasma transferrin?
Caeruloplasmin
True or False? Low concentrations of 2-3,DPG , H+ ions , Carbon dioxide and Hb S (Sicke cell anaemia ) will shift the Oxygen concentration curve to the right.
FALSE!! HIGH concentrations of all of these will shift the curve to the Right!!
What is Intravascular Haemolysis?
Intravascular Haemolysis is the breakdown of Red Blood Cells that occurs within the blood vessels/circulation.
What are the different evidences of Intravascular Haemolysis?
Gosh- Gall stones (chronic)
this
H- Haemoglobinuria. (chronic)
H -Haptoglobin decrease
H- Haemoglobinanaemia
H- Haemosiderinuria (chronic)
A- Acute tubular necrosis
A- AST increase
M- Methaemglobinaemia
M- Methaemalbuminaemia
Lunch - LDH Increase
is
Unbelievable - Urobilinogen in urine
“Gosh!!! this HHHHAMM Lunch is Really Unbelievable”
What is Extravascular Haemolysis
Extravascular Haemolysis is the breakdown of RBC’s by macrophages of the Reticuloendothelial system in liver and spleen.
What are evidences of Extravascular Haemolysis?
L - LDH increase
U - Urobilinogen in urine
S - Spelenogamaly( MAIN ONE)
A- AST increase
R- Reticulocytosis
” I LUSAR than Lucy , I sweeter than Juicy “
What are the two products after the break down of haem?
Iron (Fe2+) and Protophyron
What are the three divisions of Intrinsic Haemolysis aka (Hereditary)
Defects in RBC Metabolism
Defects in Haemoglobin Structure, function and production
Defects in RBC membrane production
“HRR Defects”
Examples of Defects in RBC metabolism.
These are the E- Enzymes
P- Pyruvate Kinase deficiency
G - G6DP deficiency
Not” ECG “but “EPG” lool
Examples of Defects in Haemoglobin structure, function and production.
Some- Sickle Cell disease
Terrible- Thalassemia
Haemoglobin - HbC disease
“Some Terrible Haemoglobin”
Examples ofdefects of RBC cell membrane production.
Please - Paroxysmal nocturnal haemoglobinuria
Help - Hereditary elliptocytosis
Henry’s- Hereditary spherocytosis
membrane
“Please Help Henry’s membrane”
What are the causes of Hereditary Spherocytosis?
Extravascular haemolysis due to defect in proteins interacting with RBC membrane skeleton + plasma membrane.
These proteins are: BAPS - Band 3 protein, Ankyrin, Paladin, Spectrin(alpha &beta)
Results: small , round RBC with no central pallor.
What are the clinical finding asscociated with Hereditary sperocytosis?
- Splenegomaly
- Aplastic crises ( Parovirus B19) infection
Test: Eosin malemide (EMA ) binding test
How does one treat Hereditary Spherocytosis?
Splenectomy
What is Hereditary Elliptocytosis?
This is a failure of spectrum heterodimers to self associate into heterotetramers . Patients with this may also present with severe haemolytic anaemia aka hereditary pyropoikilocytosis.
What is South East Asian Ovalocytosis?
This is caused by a nine amino acid deletion at the junction of they cytoplasmic and transmembrane domains of the band 3 protein.
True or false? A deficiency in G6DP mostly affects females and is carried by males?
FALSE!! It mostly affects MALES and is carried by females.
X-linked recessive
What are some causes of Intravascular heamolysis
- Mismatched blood transfusion
2.G6PD deficiency with oxidant stress
3.Red cell fragmentation syndrome
4.Some severe autoimmune haemolytic anaemia
5.Drug infected - drug Induced Haemolytic anaemia
6.Paraoxysmal nocturnal haemoglobinuria
7.March haemoflobinuria (
characterised by long walking/ running ~ might have this tbh lol) - Unstable haemoglobin
9.G6PD
What are the different causes for a G6PD deficiency?
Infections and other acute illnesses ex diabetic ketoacidosis
Drugs
Antimalarias(chloroquine)
Sulphonamides and sulphites
Other antibacterial agents
Analgesics ex aspirin
Antihelminths
Vitamin K analogues, Naphthalene, Probenecid
Fava Beans (Vica fava) contains Divicine- oxidant compound
What are the clinical findings associated with G6PD deficiency?
1.Back Pain
2.Haemoglobinuria
3.Neonatal jaundice
4. Non-spherocytic haemolytic anemia (rare)
5. Lab results - bite cells and Heinz bodies
“Stress makes me bite fava beans with Heinz ketchup”
What can a defect in the Embden-Meyerhof pathway lead to?
Non spherocytic anaemia
Which test can be used to determine G6PD deficiency and Pyruvate Kinase Deficiency
Direct Enzyme Assay
What are the features of Pyruvate Kinase deficiency?
The red blood cells become rigid because of a reduced ATP leading to extravascular haemolysis. There is also an increase in the 2,3-DPG enzyme so Oxygen affinity decreases .
What are the clinical features of Pyruvate Kinase deficiency?
- Autosomal recessive
-Jaundice - Gall stones
-Prickle cells
-Poikilocytosis (an increase in abnormal red blood cells of any shape that makes up 10% or more of the total population.)
What are the different types of Extrinsic (Acquired ) Haemolytic anaemia?
Autoimmune: Warm type Anitbodies & Cold type antibodies
Alloimmune
Red Cell fragmentation syndromes
March haemoglobinuria Infections (malaria,clostrida, babesia)
Chemical and physical agents (Drugs, Industrial/domestic substances, burns)
Secondary Diseases (liver & renal disease)
PNH