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.
Nonspecific or Innate Immunity
1. Genetic factors
- Species: Guinea pig is very susceptible to tuberculosis.
- Race: Negroes are more susceptible to tuberculosis than whites
- Sickle cells (HbS-a genetic determined Haemoglobinopathy resistant to Malarial parasite.
2. Age Extremes of age are more susceptible.
3. Hormonal status. Low resistance in:
- Diabetes Mellitus.
- Increased corticosteroid levels.
- Hypothyroidism
4. Phagocytosis. Infections can Occur in :
- Qualitative or quantitative defects in neutrophils and monocytes.
- Diseases of mononuclear phagocytic system (Reticuloendothelial cells-RES).
- Overload blockade of RES.
5. Humoral factors
- Lysozyme.
- Opsonins.
- Complement
- Interferon (antiviral agent secreted by cells infected by virus)
Pyelonephritis
- A bacterial infection that affects the renal tubules, interstitium, and renal pelvis.
- One of the most common renal diseases.
- Usually caused by gram-negative, rod-shaped bacteria that are part of the normal flora of the enteric tract. Most commonly caused by Escherichia coli, followed by Proteus, Klebsiella, and Enterobacter.
- The infecting bacteria are usually from the patient’s own enteric flora an example of an endogenous infection.
- Usually associated with a urinary tract infection (acute pyelonephritis) or involved with another precipitating condition, such as obstruction (chronic pyelonephritis).
Keratoses (Horny Growth)
1. Seborrheic keratosis is a common benign epidermal tumor composed of basaloid (basal cell-like) cells with increased pigmentation that produce a raised, pigmented, "stuck-on" appearance on the skin of middle-aged individuals.
- they can easily be scraped from the skin's surface.
- frequently enlarge of multiply following hormonal therapy.
- sudden appearance of large numbers of Seborrheic keratosis is a possible indication of a malignancy of the gastrointestinal tract (Leser-Trelat sign).
2. An actinic keratosis is a pre-malignant skin lesion induced by ultraviolet light damage.
- sun exposed areas.
- parakeratosis and atypia (dysplasia) of the keratinocytes.
- solar damage to underlying elastic and collagen tissue (solar elastosis).
- may progress to squamous carcinoma in situ (Bowen's disease) or invasive cancer.
3. A keratoacanthoma is characterized by the rapid growth of a crateriform lesion in 3 to 6
weeks usually on the face or upper extremity.
- it eventually regresses and involutes with scarring.
- commonly confused with a well-differentiated squamous cell carcinoma.
Hepatic failure
Etiology. Chronic hepatic disease (e.g., chronic active hepatitis or alcoholic cirrhosis) is the most common cause of hepatic failure although acute liver disease may also be responsible.
- Widespread liver necrosis may be seen with carbon tetrachloride and acetaminophen toxicity. Widespread steatosis is seen in Reye's syndrome, a cause of acute liver failure most often seen in children with a recent history of aspirin ingestion for an unrelated viral illness.
- Massive necrosis may also be seen in acute viral hepatitis, after certain anesthetic agents, and in shock from any cause.
Clinical features. Hepatic failure causes jaundice, musty odor of breath and urine, encephalopathy, renal failure (either by simultaneous toxicity to the liver and kidneys or the hepatorerial syndrome), palmar erythema, spider angiomas, gynecomastia , testicular atrophy
Pulmonary embolism
A pulmonary embolism (thromboembolism) occurs when a blood clot, generally a venous thrombus, becomes dislodged from its site of formation and embolizes to the arterial blood supply of one of the lungs.
Clinical presentation
Signs of PE are sudden-onset dyspnea (shortness of breath, 73%), tachypnea (rapid breathing, 70%), chest pain of "pleuritic" nature (worsened by breathing, 66%), cough (37%), hemoptysis (coughing up blood, 13%), and in severe cases, cyanosis, tachycardia (rapid heart rate), hypotension, shock, loss of consciousness, and death. Although most cases have no clinical evidence of deep venous thrombosis in the legs, findings that indicate this may aid in the diagnosis.
Diagnosis
The gold standard for diagnosing pulmonary embolism (PE) is pulmonary angiography
An electrocardiogram may show signs of right heart strain or acute cor pulmonale in cases of large PEs
In massive PE, dysfunction of the right side of the heart can be seen on echocardiography, an indication that the pulmonary artery is severely obstructed and the heart is unable to match the pressure.
Treatment
Acutely, supportive treatments, such as oxygen or analgesia
In most cases, anticoagulant therapy is the mainstay of treatment. Heparin or low molecular weight heparins are administered initially, while warfarin therapy is given
Str. agalactiae
β-hemolytic, with its capsule being the major virulence factor. Capsule inhibits phagocytosis and complement activation. The CAMP factor (a hemolysin) is another virulence factor.
Group B strep are normally found in GI tracts and vaginas.
Major disease is neonatal sepsis/meningitis after passage through infected birth canal. May lead to meningitis, and CNS damage is high. Mothers colonized with Group B strep should be treated pre-delivery.