what are the pathological changes occure during the infection with plasmodium malaria?

Answer 1

Basically, because of the peculiar life cycle of the Plasmodium spp., infection causes massive rupture of red blood cells (RBCs). This causes chills and fever, severe nausea, vomiting and diarrhea (which may resemble intestinal infections), while fever is followed by drenching sweats. Headache, convulsions, joint pain, anemia can all be signs of a Plasmodium sp. infection.

Pathologically, the most characteristic symptoms are enlarged spleen (due to congestion of sinusoids with RBCs), anemia, hemolysis, and kidney damage -- leads to hemoglobinuria (RBCs in the urine), darkening the urine (termed “blackwater fever”).

Answer 2

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Answer 3

That is a very broad question! There are many things that can go wrong. The good news is that usually NOTHING bad occurs. Most problems can be prevented from happening in the first place. A woman's body is perfectly designed to carry a baby and to give birth. Your body knows what to do! If we American women could just turn off our minds and learn to trust our bodies and trust birth it would solve a huge number of problems! (Those 'baby' shows on TV should be outlawed - they are designed to make women NOT trust birth, and to be fearful, and they set you up so that you see your doctor as rushing in to rescue you from pregnancy and birth.) If you want a healthy pregnancy and a healthy baby the best, most important prenatal care is what care you give YOURSELF. A million ultrasounds and other tests won't help anything - they only sometimes detect a problem AFTER it's a problem. So: 1. Eat right! That is the #1 thing. The idea that the baby will just take what it needs is a myth. The baby can't take it if you don't have enough of it. Nature set up YOUR body as the priority. If you don't eat right both you and your baby loose. By eat right I mean eat a well balanced diet EVERY DAY with lots of high protein foods (meat, chicken, beans, etc.), lots of vegetables and whole grains, and milk and dairy foods. Cut out (or at least down) on the empty calorie foods such as sweets, white flours, etc. 2. A good prenatal supplement is helpful, but it is NOT a substitute for eating right. 3. Don't smoke, don't be around others who smoke 4. Don't drink alcohol 5. Don't take any drugs unless prescribed by a doctor who knows you are pregnant and the benefits outweigh the risks. 6. Avoid potentially toxic chemicals, fumes, etc. 7. Get some regular exercise. If you are not used to exercising start slow. Just gentle walking is great. Prenatal yoga is good too. Exercise will make you feel better, strengthen your body, and help prepare you for birth. You will also get back into shape faster after the birth of your baby. 8. Drink plenty of water, at least 8 glasses per day. 9. Salt your food to taste. Some swelling in pregnancy is normal, especially at the end. Abnormal swelling is usually caused by inadequate protein and water in your diet, not too much salt. You need salt to grow the extra blood your body normally makes in pregnancy, and for better placental function. 10. Don't listen to the horror stories everyone wants to tell. 11. Read GOOD books during your pregnancy. a. Pregnancy, Childbirth, and the Newborn by Simkin, Whalley, Kepplar is pretty good b. The Thinking Woman's Guide to a Better Birth by Henci Goer is very good c. The Complete Book of Pregnancy and Childbirth by Sheila Kitzinger 12. See a doctor or midwife as early in pregnancy as possible. Try not to stress! Rest when tired. Trust your body.

Answer 4

The most pronounced changes related to malaria involve the blood and the blood-forming system, the spleen and the liver. Secondary changes can occur in all the other major organs, depending on the type and severity of the infection. The pathological changes are more profound and severe in case of P. falciparum malaria.

Changes in the blood

Red blood cells: Red blood cells are the principal sites of infection in malaria. All the clinical manifestations are primarily due to the involvement of red blood cells.



P. falciparum infected Red Blood Cells

The growing parasite consumes and degrades the intracellular proteins, mainly hemoglobin. The transport properties of the red cell membrane are altered, cryptic surface antigens are exposed and new parasite derived proteins are inserted. The red cell becomes more spherical and less deformable. In P. falciparum infection, membrane protuberances appear on the red cell surface in the second 24-hour of the asexual cycle. Accretions of electron-dense, histidine-rich parasite proteins are found under these 'knobs'. These knobs extrude a strain specific, adhesive variant protein of high molecular weight that mediates red cell attachment to receptors on venular and capillary endothelium, causing cytoadherence. P. falciparum infected red cells also adhere to uninfected red cells to form rosettes. Cytoadherence and rosetting are central to the pathogenesis of P. falciparum malaria, resulting in the formation of red cell aggregates and intra vascular sequestration of red cells in the vital organs like the brain and the heart. This further interferes with the microcirculation and metabolism and allows parasite development away from the principal host defense, splenic processing and filtration. As a result, in P. falciparum malaria, only younger forms of the parasite are found in the peripheral circulation and the peripheral parasitemia is usually an underestimate of the true parasite load. Mature forms of P. falciparum are rarely seen in the peripheral blood and when found, indicate severe infection. Sequestration does not occur in cases of P. vivax and P. malariae infections and therefore, all stages of the parasite can be seen in the peripheral blood and complications are very rare.

Anemia is a fairly common problem encountered in malaria and it poses special problems in pregnancy and in children. It can be due to multiple causes. Repeated hemolysis of infected red cells is the most important cause for a reduction in hemoglobin levels. Anemia depends on the degree of parasitemia, duration of the acute illness and the number of febrile paroxysms. It may occur even after 3-5 febrile paroxysms. P. vivax predominantly invades young red cells and the number of parasites infected rarely exceeds 2%. P. malariae develops mostly in mature red cells and the parasitemia is rarely greater than 1%. P. falciparum affects red cells of all ages and the parasitemia can be as high as 20-30% or more. Massive destruction of red cells accounts for rapid development of anemia in P. falciparum malaria. Immune and non-immune hemolysis of non-infected red cells, increased splenic clearance of parasitized as well as non-parasitized red cells, reduction of red cell survival even after disappearance of parasitemia, dyserythropoeisis in the bone marrow, drug induced hemolysis etc. can also contribute to the anemia. Some of these mechanisms may perpetuate anemia even after completion of the treatment.

Anemia of malaria is usually normocytic hypochromic with increase in the number of reticulocytes and polychromatophils. Rarely, atypical manifestations like macrocytic anemia or pseudoaplastic picture with pancytopenia may be seen. Anemia may be associated with hyperbilirubinemia of the indirect type, due to the hemolytic process. Splenomegaly may also be seen.

Leukocyte count is usually low to normal in most cases of malaria. Increased leukocyte count indicates either a severe infection or secondary bacterial infection. Reduction in the leukocyte count is attributed to hypersplenism or sequestration in the spleen. Relative lymphocytosis, monocytosis, eosinopenia, presence of stab neutrophils are observed with prolonged duration of the illness.

Thrombocytopenia is also fairly common in malaria. It has been observed that the platelet count shows a moderate decline during the paroxysms of fever. Thrombocytopenia may be related to the sequestration of the platelets in the spleen. Severe thrombocytopenia however indicates severe infection and may herald bleeding syndromes.

Erythrocyte Sedimentation Rate is usually elevated in malaria up to 30-50 mm in one hour. Prolonged malaria, severe anemia and severe malaria are usually associated with a higher ESR.



Bone marrow

Bone marrow may show evidence of dyserythropoeisis, iron sequestration and erythrophagocytosis in the acute phase of falciparum malaria. Maturation defects may be present in the marrow for 3 weeks after the clearance of parasitemia. Large, abnormal looking megakaryocytes have been found in the marrow and the circulating platelets may also be enlarged, suggesting dysthrombopoeisis.

Spleen

Spleen plays an important role in the immune response against malarial infection and splenectomy invariably activates a latent infection. Enlargement of the spleen is one of the early and constant signs of malarial infection. Spleen may become palpable as early as the first paroxysm.

Spleen may be palpable at the early stages of infection in the right lateral position or even in supine position. Its edge is usually round and hard to palpate and it may be tender. As the disease progresses, the spleen becomes harder, less sensitive and readily palpable. In falciparum malaria, spleen may not be palpable if the patient presents very early (due to severity). Otherwise, splenomegaly is common in all types of malaria.

The early enlargement of the spleen is due to engorgement, oedema of the pulp and later due to lymphoid and reticulo-endothelial hyperplasia with an increased hemolytic and phagocytic function of the organ. Frequent relapses and re-infections lead to pulp sclerosis and dilated sinuses.

Following treatment, spleen regresses in size, usually completely, within two weeks. In cases of large, fibrotic spleen due to repeated malaria, regression is slower, but complete involution with treatment is common.

Rapid and considerable enlargement of spleen may sometimes result in splenic rupture, which is a serious complication of malaria. This is more common in primary attack of malaria. Due to fibrosis and perisplenitis, rupture is less likely in case of chronic splenomegaly.

A small proportion of adults in Africa and India and a high proportion of adults from New Guinea have been found to suffer from huge enlargement of the spleen. This condition has been termed as the Tropical Splenomegaly Syndrome. Its nature still remains unclear. It is characterized by marked enlargement of the spleen whose weight may reach 2000-4400 g. The splenic sinuses are dilated and there is marked lymphoid hyperplasia. There is increased phagocytosis of red and white blood cells. The liver is also enlarged and shows lymphoreticular infiltration of the sinusoids. High levels of Ig G and Ig M antibodies against malaria have been demonstrated in these patients. These patients also have anemia, leucopenia, and thrombocytopenia with fairly well maintained general health. Prolonged anti malarial treatment may reduce the size of the spleen in these patients.

Liver

Enlargement of the liver also occurs early in malaria. The liver is enlarged after the first paroxysms, it is usually firm and may be tender. It is oedematous, coloured brown, grey or even black as a result of deposition of malaria pigment. Hepatic sinusoids are dilated and contain hypertrophied Kupffer cells and parasitized red cells. Small areas of centrilobular necrosis may be seen in severe cases and these may be due to shock or disseminated intravascular coagulation. Prolonged infection may be associated with stromal induration and diffuse proliferation of fibrous connective tissue. However, changes of cirrhosis are not seen. In falciparum malaria, in addition to the involvement of the mesenchyma, the hepatocytes may also be involved, causing functional changes as well (malarial hepatitis).

Malarial hepatitis is characterized by hyperbilirubinemia with elevation of conjugated bilirubin, increased levels of transaminases and alkaline phosphatase. Being part of the severe falciparum infection, it may be associated with renal failure, anemia or other complications of falciparum malaria. Liver involvement in severe falciparum malaria is due to impairment of local microcirculation associated with hepatocellular damage.

In patients with repeated attacks of malaria, liver also enlarges significantly along with a large and hard spleen. However, there is no functional abnormality of the liver in these patients. Malaria is not a proven cause for cirrhosis of the liver.

Lungs

Involvement of the lungs occurs in P. falciparum malaria and is secondary to the changes in the red blood cells and the microcirculation. Acute pulmonary oedema is an infrequent but nearly fatal complication of P. falciparum malaria, largely due to capillary endothelial lesions and perivascular oedema. Fluid overload and blood transfusion may also contribute to this problem. Pulmonary capillaries and venules are packed with inflammatory cells and parasitized red cells. The vascular endothelium is oedematous with narrowing of the lumen. Interstitial oedema and hyaline-membrane formation is also seen.

Focal or lobar pneumonia and bronchopneumonia can also complicate malaria.

Cardiovascular system

Malaria is commonly associated with cardiovascular function abnormalities. The most frequent changes during a paroxysm include decrease in blood pressure, tachycardia, muffled heart sounds, transient systolic murmur at the apex and occasional cardiac dilation. Also there is peripheral vasodilation, leading to postural hypotension.

In P. falciparum malaria, there could be microcirculatory changes in the coronary vessels. The myocardial capillaries are congested with parasitized red cells, pigment laden macrophages, lymphocytes and plasma cells.

Malaria may aggravate a pre-existing cardiac dysfunction and may prove fatal to patients already suffering from significant cardiac failure or valvular obstruction.

Gastro-intestinal tract

Malaria is often accompanied by nausea and vomiting, mainly central in origin. In the acute phase, patient may have anorexia, abdominal distention, and pain in the epigastrium. Some times the abdominal colics may be so severe as to mimic acute abdomen or appendicitis. Some patients may have watery diarrhoea and the condition may mimic gastro-enteritis or cholera.

Acute colitis may be associated with malaria. Bacillary dysentery, amoebiasis, etc. may complicate malaria.

In falciparum malaria, involvement of splanchnic microcirculation can lead to ischaemia of the gut, mucosal oedema, necrosis and ulceration. This may hamper absorption. Further these changes in the gut may also lead absorption of toxins, precipitating septic shock.

Kidneys

Malaria can cause varied problems in the kidneys. During the acute attack, albuminuria may be seen commonly. Acute diffuse malarial nephritis with hypertension, albuminuria and oedema may also be seen rarely.

In P. malariae infection, nephrotic syndrome may be seen (Quartan malaria nephropathy). This immune complex mediated nephropathy develops weeks after the malarial illness and is characterized by albuminuria, oedema and hypertension. It may be progressive and may require treatment with steroids or immunesuppressants.

In severe P. falciparum malaria, acute renal failure may develop in 0.1-0.6% of the patients. Microcirculation disorders, anoxia and subsequent necrosis of the glomeruli and renal tubules are responsible for this serious complication. Disseminated intravascular coagulation also may cause or aggravate this problem.

Central nervous system

Central nervous system manifestations in malaria could be due to pathological involvement of the brain, paroxysms of fever or due to the side effects of antimalarial drugs.

The febrile paroxysms are usually accompanied by head aches, vomiting, delirium, anxiety and restlessness. These are as a rule transient and disappear with normalization of the temperature.

Antimalarial drugs like chloroquine, quinine, mefloquine and halofantrine can cause various symptoms like dizziness, vertigo, tinnitus, restlessness, hallucinations, confusion, delirium or even frank psychosis, convulsions etc. Quinine can induce hypoglycemic coma. Artemisinin derivatives are known to cause brain stem dysfunction in animal studies. These factors should always be kept in mind while managing cases of malaria.

Nervous system gets involved predominantly in P. falciparum malaria and only very rarely in the other forms. Decreased deformability, increased cytoadherence and rosetting of red cells, occlusion of the microcirculation by the red cell rosettes and their thrombosis- all these result in cerebral anoxia, development of malaria granulomas and punctate haemorrhages leading to malarial encephalitis and meningoencephalitis. At autopsy, the brain is found to be oedematous; small blood vessels are congested with parasitized red cells; the surface of the brain appears leaden or plum coloured while the cut surface has a slatey-grey hue. Up to 70% of the red cells in the brain may be found to be parasitised, and many mature forms of the parasite including schizonts could be seen. In larger vessels, the parasites form a layer along the endothelium, called as 'margination'. The vascular endothelium shows pseudopodial projections, which may be in close apposition to the 'knobs' on the surface of the parasitized red cells. Numerous petechial haemorrhages are found in the white matter, proximal to the occlusive plugs in the end arterioles. Dürck's granulomata, small collections of microglial cells surrounding an area of demyelination may be seen at the site of these haemorrhages.