Anaemia Flashcards
What is anaemia
Decrease in RBC to a level that’s insufficient for respiration
Or decrease in O2 carrying capacity of blood
Decrease in the Hb conc, to a level where O2 delivery becomes compromised
When does O2 delivery become compromised in adult Male and female
When Hb conc is less than 13g/DL for male
12g/dL for women
When does O2 delivery become compromised for children
When Hb is less than 12g/dL (4-16 yrs)
11g/dL (30days- 6yrs)
13..5g/dL (0-30days)
What volume of O2 does 1g of Hb bind
1.34ml of O2
If the Hb conc ie 15g/dL , what’s the volume of O2 that can be carried
1.34 (for 1g of Hb) X 15
= 20ml
What is oxygen tension
The amount of O2 present in 100ml of blood
What is the normal O2 tension
20ml. (1.34 X 15)
What happens to O2 tension with reduction in Hb concentration
Reduces
What’s the partial pressure of O2 when the O2 tension is 20%
100mmHg
What’s the normal Hb conc, O2 tension and partial pressure in 100ml of blood
Hb conc: 15g/dL
O2 tension : 20 volume %
Partial pressure of O2: 100mmHg
What is the partial pressure of O2 in blood if the O2 tension falls from 20-15 volume%
It falls from 100mmHg to 40mmHg
When the O2 tension in the artery is 20volume% whats the O2 tension in the veins
15volume%
What’s the areterovenous O2 difference
5volume%
In every 100ml of blood, how much O2 is given to tissue and how much is retained
5volume% is given to tissue and 15volume% is retained
In every 100 ML of blood how much oxygen is given to the tissue and how much is it retained?
5ml is given to the tissue and 15ml is retained
What happens when an individual HB concentration is as low as 10 g/dL
The arterial partial pressure would fallen lower than the Venous partial pressure of oxygen hence, the pression gradient that’s allows oxygen to be driven tissue is lost.
If the Hb conc is 10g/dL, that means the O2 tension is 13.4volume% (instead of the normal 20volume% from 15g/dL Hb)
What happens when the Hb conc, the O2 tension and the O2 PP all reduce
The body adapts and tries to find a way to get O2 to all the pets of the body
What are the 5 adaptations to anaemia
•Modulation Hb/O2 affinity
•CVS adaptive mechanism
•Redistribution of blood flow
•Widen arterovenous O2 difference (by reducing venous O2 tension below 15volume%)
What kind of carrier of O2 is Hb
A reversible carrier
Binds to O2 at high O2PP but readily parts at low O2PP
What is high O2 affinity Hb
An abnormal Hb that has excessive affinity for O2
Complex with O2 at high or low PP ma don’t part , hence there could be Hb conc, but low O2 for tissues
What is Low O2 affinity Hb
An abnormality where the Hb has excessively low affinity for O2 hence only binds under excessively high PP of O2
The little O2 they have is delivered to tissues but it’s not enough
What happens to the affinity of O2 for Hb in anemia
Reduced
What pathway does RBC use to make ATP under normal conditions
Glycolytic pathway (Embden-meyerhof)
G3P—1,3DPG—3PG
What happens to O2 when it complexed with Hb
Emits a proton (to be acidic, hence in the absence of enough O2, the cytoplasm is alkaline)
In Anemia, what does the RBC produce
Hb instead of ATP
Converting 1,3DPG to 2,3 DPG by 1,3DPG mutase - then from 2,3 DPG TO 3 PG by 2,3 DPG phosphatase Rapport- Luebering shunt
Instead or 1,3DPG to 3PG directly(to produce ATP)
What pathway tries to help to pass O2 to tissues in anemic conditions
Energy clutch pathway/ Rapport Luebering shunt
What feature of the RBC cytoplasm stimuthates conversion of 1,3DPG to 2,3DPG
The alkalinity in anemic situations
What’s the function of 2,3DPG
It’s is capable of complexing with Hb and allow O2 detach from Hb at low O2 PP (to the tissues)
What’s the most adaptive mechanism of anemia
The generation of 2,3DPG
What makes the cytoplasm alkaline in anemia
The presence of HHb instead of HbO2 in the cytoplasm
What is the CVS adaptive mechanism of anemia
•Increased vascular dilatation
•Decreased peripheral resistance
•Myocardial dilatation (increased volume of the 4 chambers)
•Increased HR
•Increased CO
What’s the O2 tension of 5L of blood (physiological CO)
100ml—20 ml
5000ml—X
X= 1000ml O2 carrying capacity(available to tissues per minute) of 5L of blood
Of the 1000ml of O2 available to the body per minute, what goes to the brain, myocardium, muscle and the whole body
The body only requires 250ml
•60ml - Brain
•50ml- myocardium
•60ml- muscle mass
And the rest distributed
Which parts of the body are O2 sensitive
Brain, Heart, Skeletal muscle
What happens to the O2 distribution if the Hb conc was 10g/dL instead of 15g/DL
The HR would have increased to ~ 100 instead of 72 and the SV would be ~ 100 instead of 70
The CO would be like 10L instead of 5L
So instead of having 1000ml of O2 available for distribution, there would be 1340ml available (replacing 13.4 for 20, and 10L for 5L in the calculation)
Compare the CVS adaptation and the Modulation of Hb/O2 affinity
They are both equall vital but the CVS adaptation has energy implications and could easily fail if Hb clc falls extremely low
The failure of CVS adaptation is usually the cause of death in severe anemia
When will the CVS adaptation fail
When the Hb conc goes lower than 7g/dL
However in children under 5, it may not fail till the Hb conc is as low as 5g/dal
What is severe anemia
When the Hb conc is lower than 8g/dL
Features of failure of CVS adaptation
•Fast HR (greater than 100-120bpm)
•Biventricukar heart failure
• Redistribution of blood flow
• More capillaries are opened up
Features of biventricular heart failure (Right and Left)
Right ventricular Heart failure
•Raised Jugular pressure
•Hepatomegaly
•Ascitis
•Gravity Dependent pedal edema
Left ventricular heart failure
•Pulmonary edema (Basal crepitations on ascaultation due to fluid at the base of lung : Heamic murmur) ;chokes to death
Explain redistribution of blood flow
Redistribution of blood to more O2 sensitive areas at the expense of O2 less send areas
What part of the body is less O2 sensitive
Predominantly the skin
Also kidney (only needs 4ml per minute instead of 100 that’s given to it)
Explain the opening of more capillaries
•This is to ensure tissues are better perfused
•There’s more plasma that RBC drying anemia , makes the blood more viscous hence need more push (reduced peripheral resistance helps)
If the cause of the anemia is not due to bone marrow failure, why other mechanism can be used to adapt
Compensatory increase of erythropoesis as sim in sickle cell anemic patients
What’s the classification of anemia
•Morphological classification
•Etiological classification
What is the morphological classification of anemia
refers ot the physical appearance of red cell together with the red cell indices as the base of classification
What are the three types of anemia based on morphological classification
•MACROCYTIC normochromic anemia
•Microcytic hypochromic anemia
•Normocytic normochromic anemia
What is macrocytic normochromic anemia
Large RBCs with normal Hb on them
As a result of impairment of DNA synthesis but not impairment of RNA transcription
What’s another name for macrocytic normochromic anemia
Megaloblastic anemia
What is Microcytic hypochromic anemia
Small cell size with small Hb content
As a result of impairment of Hb synthesis, deficiency of iron, or failure of iron utilization
Explain normocytic normochromic anemia
•Normal cell size and normal Hb content
•Associated with chronic disorders
•Also called **Anemia of chronic disorder **
What are the types of anemia based on the etiologies classification
•Anemia of blood loss/Hemorrhagic anemia
•Anemia of decreased RBC/Hemolytic anemia
•Anemia of bone marrow survival failure
Explain Hemorrhagic anemia
•Blood loss could be acute or chronic
Acute hemorrhagic anemia
-Acute obstetric hemorrhage
-Disseminated Intravascular coagulopathy
-Post partum hemorrhage
-Bleeding from animal poison
Chronic hemorrhagic anemia
-Hematomosis (bleeding from mouth)
-Hemoptosis (coughing blood)
-Epistasis (sneezing blood)
-Bleeding stool
What’s the most common cause of hemorrhage all over the world
Road traffic accident
Others include, violent injuries, injuries from building collapse
Explain acute obstetric hemorrhage
-Placenta Previa (cause of antepartum hemorrhage)
-Abruptio placenta
-Ectopic gestation
-Uterine rupture
Causes of post partum hemorrhage
-Placenta retention
-Uterine atomy
What causes Hematemesis
This is bleeding from mouth, includes vomiting blood
-Gastric ulceration
-Duodenal ulcers
-Gastric carcinoma
-Bleeding from esophageal varices
Causes of hemoptosis
This is coughing blood
-Chronic chest infection
-Collagen Wagener’s granulomatosis
-Heart failure
-Pulmonary infarction
-Lung/Bronchial cancer
Causes of epistasis
This is sneezing blood
-Weakened or loss of integrity of vessels
-Severe hypertension
-Systemic diseases (thrombocytopenia)
-impairment of platelet function
Causes of Hematochezia
This is bleeding in stool
-upper GIT bleeding
-Lower GIT bleeding
What’s the characteristic of upper GIT bleeding
Malena stooling - dark colored foul smelling
Same causes as hematemesis
Causes of lower GIT bleeding
Bleeding hemorrhoids
Colonic diverticulosis
Anal tear
Colonic/ceacal carcinoma
Inapparrnt GIT blood loss
What causes in apparent GIT blood loss
Blood sucking intestinal parasites (hookworm)
Causes of Hematuria
Bleeding into the urethra
-pathology in bladder, kidney , urethra , ureter
Kidney pathology
•payelonephrotis
•Renal papillary necrosis (ss)
•Carcinoma
Ureter pathology
•Ureteric stones (leading to erosion)
Bladder pathology
•Infections (schistosoma hematobium)
•Carcinoma
•Stones (erosions)
Irethra pathology
•Obstruction/Fibrosis ( from gomococcal infection)
Causes of Memoragia
This is vaginal bleeding
-Vaginitis
-Cervicitis
-Cervical cancer
-Fibroid
-Endometriosis
-Endometrial cancer
-Dysfunctional uterine bleeding
Causes of Hemathrosis and Hematoma
Hemathrosis- Bleeding into joints
Hematoma- Bleedimg into soft tissue
-Coagulative protein disorder
Causes of Purpura
This is bleeding into skin
-Platelet disorder
-VW disease
-Vascular collagen disorder (Ehler Dahlos syndrome )
What % of RBC are removed and replved daily
~1%
What is hemolytic anemia
When the life span of RBC is shorten to as low as 20 days ( seen in HbSS) or 50-60 days (seen in HbSC)
And the bone marrow’s ability to increase production RBC and Hb conc is impaired
What are the 2 causes of hemolytic anemia
Intracapsular pathology
Extracapsular pathology
What are the 2 types of intracapsular pathology
-Cell membrane pathology
-Cytoplasmic pathology
What are the 2 types of RBC membrane pathology
Acquired and Inherited membrane pathology
What causes acquired RBC membrane pathology
•As a result of paroxysmal nocturnal hemoglobinurea (PNH) due to deficiency of decay attack mechanism (perforated proteins lose the membrane)
• Also as a result of Zeid’s triad
What does the Zeids triad consist of
Alcoholic Liver disease
Hyperlipidemia
Hemolytic anemia
Who is an alcoholic
Takes at least 80g of alcohol daily
How does the Zeids triad come about
Because of the liver disease, liver cannot oxidize the lipids to form energy, then the lipid go back into the blood causing hyperlipidemia , then it goes into the cell causing too much lipid in the cell then causing lyses
What are the types of Inherited RBC membrane pathology
•Inherited spherocytocis
•Inherited acanthocytosis
•Inherited stomatocytosis
•Inherited ovalocytosis
•Inherited elliptocytosis
•Inheritedpyropoikilocytosis
A as what are the 2 types of cytoplasmic pathology
Enzymopathies
Hemogliobinopathy
What are the 2 types of enzymopathy
Deficiency of enzyme in glycolysis
Deficiency of enzymes in reducing pathway
What enzymes are deficient in glycolytic enzymopathy
All the enzymes can be deficient but the commonest is hexokinase and pyruvate kinase
What does deficiency of glycolytic enzymopathy lead to
Leads to reduction in ATP generation
Which causes Na/K ATPase failure, hence Na influx and Water influx , which leads to is osmotic cell lyses
What is the reducing power of RBC
NADPH2
Why does RBC need NADPH2
It is required by RBC to reduce oxidized membrane macromolecules including membrane proteins and membrane lipids
When do we say a carbon atom is fully reduced
When the valency points is fully occupied by H atom
What happens when a reduced carbon atom is oxidized
We want carbon atoms to be full reduced
When a oxidizing molecule is brought to a reduced carbon, it changes its single bonds to double bonds and makes it easy to break
With each oxidation, it’s easier to break, causing membrane lipid / protein damage
What does the RBC use to reduce oxidized membrane macromolecules
What is Glutathione
A tripeptide consisting of Glutamine, Cysteine, Methionine
What 2 enzymes does the RBC use to synthesize the GSH and their role
•Gamma-glutamyl-cysteinyl-transferase- Joins Glutamime to cysteine
•Glutathione synthase - Add methionine to the glutamine, cysteine comples
How does the GSH help reduce oxidizes macromolecules
It’s gives of its H atom to the oxidized molecule and becomes an unstable G-S
Then two G-S fuse to become a stave G-S-S-G , a stable oxidized glutathione
What enzyme links tow unstabe G-S to stabilize it G-S-S-H
Glutathione peroxidase
What enzyme helps to fuse the unstable G-S to stabilize it to G-S-S-G
Glutathione peroxidase
Why does the oxidized glutathione (G-S-S-G) have to get reduced back to GSH
Because the RBC does not have tha capacity to keep synthesizing new GSH
What converts the oxidized G-S-S-G back to a reduced GSH
RBC reducing power NADPH2 (and then becomes NADP)
What enzyme does RBC use to reduce oxidized membrane macromolecule
Glutathione
What enzyme converts the oxidized G-S-S-G back to a reduced GSH
Glutathione reductase
How is the oxidized NAPD reduces back to NADPH2
Glucose-6-phosphate is converted to 6-phosphoglutamate using G-6-P dehydrogenase
What’s the most important enzyme in producing reducing power
Glucose-6-phosphate dehydrogenase (converts G-6-P to 6-phosphoglutamate and produces NADPH2)
What happens to people deficient in G-6-P dehydrogenase
They cannot reduce oxidized NADP which in turn cannot reduce oxidized glutathione which in turn cannot reduce oxidized membrane macromolecules
List all the enzymes involved in the reducing pathway of RBC
•Gamma-Glutamyl-Cystyl-trasferase
•Glutathione synthase
•Glutathione peroxidase
•Glutathione reductase
•Glucose -6-phosphate dehydrogenase
