NEET MDS Lessons
General Pathology
Nephrotic Syndrome
The patient will present with a triad of symptoms:
- Proteinuria, i.e. >3g/24hr-3.5g/24 hr
- Hypoalbuminaemia, i.e. <30g/L
- Oedema
>80% of cases are due to glomerulonephritis. In this syndrome, there is damage to podocytes
Clinical signs
- Pitting oedema, particularly in the limbs and around the eyes; may also cause genital oedema and ascites.
- Possible hypertension
Causes
- Primary causes – these are diagnoses of exclusion that are only made if secondary causes cannot be found
o Minimal change disease (MCD)
o Focal segmental glomerulosclerosis
o Membranous nephropathy
- Secondary causes – note that these fall into the same three categories as above:
o Minimal change disease – Hep B, SLE, diabetes M, sarcoidosis, syphilis, malignancy
o Focal segmental glomerulosclerosis –HIV, obesity, diabetes M, hypertensive nephrosclerosis
o Minimal change disease –drugs, malignancy, particularly Hodgkin’s lymphoma
- Differential diagnoses include cardiac failure, i.e. increased JVP, pulmonary oedema and mild proteinuria, and liver disease, i.e. reduced serum albumin.
- The condition causes an increased susceptibility to infection – partly due to loss of immunoglobulin in the urine. Patients tend to be prone to streptococcus infection, as well as bacterial peritonitis and cellulitis.
- Nephrotic syndrome also increases the risk of thromboembolism and hyperlipidaemia.
- The former is due to an increase in the synthesis of clotting factors and to platelet abnormalities, and the latter is a result of increased synthesis of these by the liver to counteract reduced oncotic pressure.
Investigations
- These are the same as those carried out in GN.
- Also, check for cholesterol as part of confirming the presence of hyperlipidemia.
- Renal biopsy – order this for all adults. In children, because the main cause is minimal change GN, steroids are the first-line treatment. Therefore, in children, biopsy is necessary only if pharmaceutical intervention fails to improve the situation.
- The hypercoagulant state seen in the nephrotic syndrome can be a risk factor for renal vein thrombosis. This can present as loin pain, haematuria, palpable kidney and sudden deterioration in kidney function. This should be investigated with Doppler USS, MRI or even renal angiography.
- Once diagnosed, give warfarin for 3 to 6 months.
Management
- Generally, this involves treatment of the underlying condition which is usually GN. Therefore, fluid management and salt intake restriction are priorities. The patient is usually given furosemide along with an ACE inhibitor and/or an angiotensin II receptor antagonist. Prophylactic heparin is given if the patient is immobile. Hyperlipidaemia can be treated with a statin.
Nephritic Syndrome
Acute and chronic
forms of the syndrome exist. The main difference between this and nephrotic syndrome is that in nephritic syndrome haematuria is present. There is also proteinuria, hypertension, uraemia, and possibly oliguria. The two standout features are hypertension and RBC casts. The urine will often appear ‘smoky’ in colour due to the presence of RBC casts. Very rarely, it may appear red
Causes
1. Post-streptococcal
2. Primary:
- Membranous glomerulonephritis
- Rapidly progressive glomerulonephritis
- IgA nephropathy (Berger’s disease)
3. Secondary
- HSP
- Vasculitis
Clinical Features
- Abrupt onset of :
o Glomerular haematuria (RBC casts or dysmorphic RBC)
o Non-nephrotic range proteinuria (< 2 g in 24 hrs)
o Oedema (periorbital, sacral )
o Hypertension
o Transient renal impairment (oliguria, uraemia)
- Urinary casts – these are cylindrical structures produced by the kidney and present in the urine in certain renal diseases. They form in the DCT and collecting duct, dislodging and passing in the urine where they are detected by microscopy. RBC casts are usually associated with nephritic syndrome. The presence of RBCs within a cast is always pathologic and strongly indicative of glomerular damage.
- The proteinuria present is often smaller than in nephrotic syndrome, thus a coexistent condition of nephrotic syndrome is not usually present.
- Encepelopathy may be present, particularly in children, due to electrolyte imbalances and hypertension. This type of presentation is indicative of glomerular damage, but requires renal biopsy to determine the exact problem. In this respect it is similar to nephrotic syndrome.
Overlapping of the two syndromes is possible as nephrotic syndrome may precede nephritic syndrome, although not vice-versa.
Mechanisms of the syndrome vary according to cause; both primary and secondary causes exist. Post-infectious GN is the classic illustration of nephritic syndrome, but the condition may be caused by other glomerulopathies and by systemic diseases such as connective tissue disorders
Two clinical terms to remember:
- Nephritic syndrome; which comprises edema, proteinuria, hypoalbuminemia, hematuria (smoky urine), oligurua and hypertension.
- Nephrotic syndrome; which comprises of albuminuria, hypoalbuminemia, edema, hyperlipidemia, lipiduria.
Asthma
Asthma is
(1) An obstructive lung disease characterized by narrowing of the airways.
Inflammation of the airways is a major component of asthma.
(2) Common symptoms are dyspnea, wheezing on expiration, and coughing.
(3) Two types:
(a) Extrinsic (allergic, atopic) asthma
(i) An atopic allergy caused by a type I immediate hypersensitivity immune reaction to an allergen.
(ii) Seen in children, adults.
(b) Intrinsic (nonallergic) asthma
(i) Not caused by an allergic reaction.
(ii) Mostly seen in adults.
The disorder is a chronic inflammatory condition in which the airways develop increased responsiveness to various stimuli, characterized by bronchial hyper-responsiveness, inflammation, increased mucus production, and intermittent airway obstruction.
Signs and symptoms
- The clinical hallmarks of an attack are shortness of breath (dyspnea) and wheezing
- A cough—sometimes producing clear sputum—may also be present
- The onset is often sudden; there is a "sense of constriction" in the chest, breathing becomes difficult, and wheezing occurs
- Signs of an asthmatic episode are wheezing, rapid breathing (tachypnea), prolonged expiration, a rapid heart rate (tachycardia), rhonchous lung sounds (audible through a stethoscope), and over-inflation of the chest.
- During very severe attacks asthma sufferer can turn blue due to lack of oxygen , can experience chest pain or even loss of consciousness, may lead to respiratory arrest and death
Pathophysiology
Bronchoconstriction : asthma is the result of an abnormal immune response in the bronchial airways. The airways of asthmatics are "hypersensitive" to certain triggers, also known as stimuli, these stimuli include allergens, medications , air pollution, early child hood infection, exercise, emotional stress
Bronchial inflammation asthma resulting from an immune response to inhaled allergens—are the best understood of the causal factors. In both asthmatics and non-asthmatics, inhaled allergens that find their way to the inner airways are ingested by a type of cell known as antigen presenting cells These activate an humoral immune response. The humoral immune system produces antibodies against the inhaled allergen. Later, when an asthmatic inhales the same allergen, these antibodies "recognize" it and activate a humoral response. Inflammation results: chemicals are produced that cause the airways to constrict and release more mucus, and the cell-mediated arm of the immune system is activated. The inflammatory response is responsible for the clinical manifestations of an asthma attack
Symptomatic Treatment
Episodes of wheeze and shortness of breath generally respond to inhaled bronchodilators which work by relaxing the smooth muscle in the walls of the bronchi., More severe episodes may need short courses of inhaled, oral, or intravenous steroids which suppress inflammation and reduce the swelling of the lining of the airway.
Bronchodilators (usually inhaled)
Short-acting selective beta2-adrenoceptor agonists(salbutamol, terbutaline)
less selective adrenergic agonists, such as inhaled epinephrine and ephedrine tablets
Antimuscarinics
Systemic steroids
Oxygen to alleviate the hypoxia that is the result of extreme asthma attacks.
If chronic acid indigestion ( GERD) is part of the attack, it is necessary to treat it as well or it will restart the inflammatory process
Preventive Treatment
most effective preventive medication are
Inhaled corticosteroids
Long-acting beta2-adrenoceptor agonists
Leukotriene modifiers
Mast cell stabilizers
Methylxanthines (theophylline and aminophylline),
Antihistamines, often used to treat allergic symptoms
Acute viral hepatitis
Clinical features. Acute viral hepatitis may be icteric or anicteric. Symptoms include malaise, anorexia, fever, nausea, upper abdominal pain, and hepatomegaly, followed by jaundice, putty-colored stools, and dark urine.
In HBV, patients may have urticaria, arthralgias, arthritis, vasculitis, and glomerulonephritis (because of circulating immune complexes). Blood tests show elevated serum bilirubin (if icteric), elevated transaminases, and alkaline phosphatase.
The acute illness usually lasts 4-6 weeks.
Pathology
(1) Grossly, there is an enlarged liver with a tense capsule.
(2) Microscopically, there is ballooning degeneration of hepatocytes and liver cell necrosis.
Cells Of The Exudate
Granulocytes (Neutrophils, eosinophils, and basophils)
Monocytes (and tissue macrophages)
Lymphocytes
Neutrophils (polymorphs).
Characteristics
(1) Cell of acute inflammation.
(2) Actively motile.
(3) Phagocytic.
(4) Respond to chemotactic agents like.
Complement products.
Bacterial products.
Tissue breakdown
Lysosomal enzymes of other polymorphs
Functions
(1) Phagocytosis and intracellular digestion of bacteria.
(2) Exocytosis of lysosomal enzymes to digest dead tissue as the first step in the process of repair.
Eosinophils
Characteristics
(I) Cell of allergjc and immunologic inflammation.
(2) Motile and phagocytic but less so than a neutrophil.
(3) Response to chemotaxis similar to neutrophil. In addition, it is also responsive to antigens and antigen-antibody complexes.
(4) Steroids cause depletion of eosinophils.
Functions
(1) Contain most of the lysosomal enzymes that polymorphs have
(2) control of Histamine release and degradation in inflammation
Basophils (and mast cells)
Characteristics
(1) Contain coarse metachromatic granules.
(2) Contain, histamine and proteolytic enzymes
Functions
Histamine: release which causes some of the changes of inflammation and allergic
reactions. .
Monocytes .
Blood monocytes form a component of. the mononuclear phagocytic system (MPS), the other being tissue macrophages The tissue macrophages may be :
(a) Fixed phagocytic. cells:
- Kuffer cell of liver.
- Sinusoidal lining cells of spleen and lymph nodes.
- Pleural and peritoneal macrophages
- Alveolar macrophages.
- Microglial cells.
(b) Wandering macrophages or tissue histiocytes.
The tissue histiocytes are derived from blood monocytes.
Characteristics
.(1)Seen in inflammation of some duration, as they -outlive polymorphs.
(2) Actively phagocytic and motile.
(3) Fuse readily to from giant cells in certain situations.
Function
(1) Phagocytosis.
(2) Lysosomal enzyme secretion.
(3) Site of synthesis of some components of complement.
(4) Antigen handling and processing before presenting it to the Immune competent cell.
(5) Secretion of lysosyme and interferon.
Giant cells can be
(A) Physiological
Syncytiotrophoblast, megakatyocytes, striated muscle, osteoclast.
(B) Pathological:
Foreign body: in the presence of particulate foreign matter like talc, suture material etc. and in certain infections_e g fungal.
Langhan's type: a variant of foreign body giant cell seen in tuberculosis.
Touton type in lipid rich situations like Xanthomas, lipid granulomas etc.
(iv) Aschoff cell in rheumatic carditis.
(v) Tumour gjant cells e.g. Reid-Sternberg cell in Hodgkin's Lymphoma, giant cells in any malignancy.
Lymphocytes and Plasma cells
These are the small mononuclear cell comprising the immune system
They are less motile than_macrophages and neutrophils and are seen in chronic inflammation and immune based diseases.
A dermatofibroma is a benign tumor of the dermis, MC located on the lower extremity, where it has a nodular, pigmented appearance.
- composed of benign histiocytes.
Microbiological examination
This is a method by which body fluids, excised tissue, etc. are examined by microscopical, cultural and serological techniques to identify micro-organisms Microbiological examination responsible for many diseases.
Wilson’s disease
Caused by a decrease in ceruloplasmin, a serum protein that binds copper, resulting in metastatic copper deposits.
Common organs affected include:
(1) Liver, leading to cirrhosis.
(2) Basal ganglia.
(3) Cornea, where Kayser-Fleischer rings (greenish rings around the cornea) are observed.